SAHA对人宫颈癌细胞化放疗增敏作用的研究
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摘要
目的：观察组蛋白去乙酰化酶抑制剂：SAHA (suberoylanilide hydrox amic acid)联合顺铂或X射线照射后人宫颈癌SiHa细胞生长抑制、细胞凋亡、细胞集落形成率等情况,探讨SAHA(?)寸宫颈癌细胞化疗和放疗增敏的效果。同时检测(?)P21、Bax及Ku70的mRNA和蛋白的表达,探讨其增敏的机制。
方法：1、以SAHA0.25、0.5、1、2、4、6μ mol/L和DDP1、2、4、6、8、10μg/mL分成单药组和不同浓度SAHA+DDP联合用药组,另设不加药对照组,作用于体外培养的人宫颈癌SiHa(?)细胞。采用MTT比色法检测各组SiHa细胞的增殖抑制率；流式细胞术检测各组的细胞周期；用AnnexinV-FITC标记药物作用后的细胞,了解其早期凋亡的情况；2、20%IC50SAHA预处理SiHa细胞24h后与不同剂量X射线(0Gy、1Gy、2Gy、4Gy、6Gy、8Gy)联合,利用细胞克隆形成实验检测照射后集落形成率,并计算细胞存活分数；根据单击多靶模型SF=1-(1-e-D/Do。)n拟合生存曲线并计算外推值,平均致死剂量和准阈剂量以及放射增敏比；3、用RT-PCR法和Western blot法分析药物作用及射线照射后宫颈癌细胞中P21、Bax和Ku70的mRNA和蛋白的表达；
结果：1、SAHA(?)单药处理细胞时,各组对SiHa细胞的生长抑制率均比对照组升高(P<0.05)；随着给药时间延长,细胞的生长抑制率逐渐升高(P<0.05)。2、SAHA与DDP联合作用SiHa细胞24h,不同剂量联合组对细胞的抑制率均较单用DDP明显(P<0.05)；与1、2、4ug/ml DDP联合应用时,随SAHA剂量的增大抑制率逐渐增高(P<0.05)；SAHA在剂量浓度为1、2、4μ mol/L时,细胞的抑制率随DDP浓度的增加而升高；联用的效果Q值显示SAHA和相对中低剂量的DDP联合用药表现为协同作用,较高剂量的DDP联合用药为单纯相加作用。3、SAHA1、2、4μ mol/L(S组)分别与DDP1、2、4ug/ml(D组)联合(SD组)作用于SiHa细胞,与对照组比较,S组、D组及SD组G0/G1期比例明显增加,而G2/M+S期细胞比例明显减少,PI明显下降(P<0.05)；与S及D组比较,SD组G0/G1期比例明显增加,而G2/M+S期细胞比例明显减少,PI明显下降(P<0.05)；4、各联合组早期凋亡细胞比例均较单药组明显升高(P<0.05)；在2μ g/ml的DDP作用SiHa细胞24h后,细胞凋亡不明显,但经2μ mol/L SAHA预处理后,细胞凋亡率显著增加,且随着SAHA浓度的增加,凋亡率也增加(P<0.05)。5、Bax mRNA及蛋白在S、D组表达比较微弱,与对照组比较无差异(P>0.05),联合作用后BaxmRNA及蛋白的表达显著高于其他各组(P<0.05)；6、P21mRNA及蛋白在各组的表达均上调,以联合组的表达上调显著,明显高于D组和对照组(P<0.05)。7、SAHA联合照射组的细胞存活分数明显低于单独放疗组,随放疗剂量的增高,细胞存活分数逐渐降低(P<0.05)；利用多靶单击数学模型绘制出细胞辐射存活曲线,可见联合组曲线较单纯照射组左移,且较为平直、“肩区”不明显。单独照射组和联合组平均致死剂量Do分别为2.329、1.213,外推数N分别为2.761、4.770,准阈剂量Dq分别为1.721、0.823。放射增敏比为1.92。8、SAHA组BaxmRNA及蛋白的表达与对照组比较差异无统计学意义(P<0.05)，照射组明显高于对照组(P<0.05),SAHA联合照射组明显高于其它各组(P<0.05)；SAHA(?)关合照射组细胞Ku70mRNA及蛋白的表达明显低于照射组(P<0.05)；
结论：1、SAHA在体外能够抑制人宫颈癌SiHa (?)细胞的生长,抑制作用呈时间剂量依赖性。2、SAHA联合DDP作用SiHa细胞,在体外可以显著诱导细胞凋亡,并使细胞周期阻滞于GO/G1期,二者具有协同作用。3、SAHA联合DDP作用SiHa细胞,能够显著地上调p21、Bax的mRNA及蛋白表达水平,可见促进细胞凋亡及阻断细胞周期可能是SAHA (?)曾强SiHa细胞对DDP敏感性的机制之一。4、小剂量SAHA在体外能够促进SiHa细胞对X-线照射的敏感性。5小剂量SAHA通过增加放射诱导细胞凋亡基因Bax的表达及下调DNA修复基因Ku70的表达,促进了细胞的凋亡,抑制了细胞的修复,从而实现对SiHa(?)细胞的放射增敏作用。
Objective
To observe the sensitizing effects of the HDAC inhibitor suberoylanilide ydroxamic acid (SAHA) combined with DDP or X ray to cervical cancer SiHa cells and the mechanism of sensitization as well through studying the growth inhibition and apoptosis, cell colons formation rate and the result of the radiation sensitive parameters of cerical cancer cells.
Methods
1. SiHa cells were treated with0.25,0.5,1,2,4and6μmol/L of SAHA, and1.2,4,6,8and10μg/mL of DDP, respectivly. SiHa cells were treated with the vary combination dose of the two drugs. The inhibitory rate of SiHa cells were analyzed with MTT; Cell cycle distribution was detected by flow cytometry; Apoptosis of cells was measured by Annexin V-FITC.2. SiHa cells were incubated with SAHA at the concentration of20%IC50for24h and then were exposed to X-ray irradiation (IR)(0,2,4,6,8Gy). Colonies and surviving fraction (SF) of cells were detected by Clonogenic assay, the SF、Do and sensitizing enhancement ratio (SER) of each groups and the cell survival curve was gained by single-hit multi-target model.3. P21, Bax and Ku70's mRNA and protein expression levels were investigated by RT-PCR and Western bolt in SiHa cell. Results
1. SAHA was capable of inhibiting SiHa cells growth comparing with control group (P<0.05); SAHA appears more inhibiting SiHa cells growth effect attending by the increasing dose and time.2. The combined groups inhibited the cell growth obversely than single drug groups after24hours (P<0.05); Inhibition rate increased gradually with SAHA increasing dose combined with DDP; The effect of SAHA combined With DDP showed that low doses of DDP combination is synergy, while higher doses of DDP combination has simple addition effect.3. When1,2,4umol/L of SAHA (S group) combined with the DDP1,2,4ug/ml (D group) respectively, all the groups appear arresting cell at G1/G0phase, while the G2/M+S period cells proportion markedly reduced. PI reduced compared with control group significantly (P<0.05). GO/G1phase ratio increased significantly in SD group, while the G2/M+S period cells proportion markedly reduced. PI reduced significantly compared with the S group and D group (P<0.05).4. SAHA combing with DDP induced more severe apoptosis than separate groups (P<0.05). Apoptosis in2ug/mL DDP group was not obviously, but after pretreatment by2umol/L SAHA, apoptosis rate increased significantly.5. Compared the expression of Bax mRNA with the control group, there was no statistical significance of D, S group(P>0.05), while the expressions of combination groups were higher then other groups(P<0.05); P21expression in each group is raised significantly, especially in combination groups comparing with D group and control group (P<0.05).6. Bax protein expression between SAHA groups and the control group was not statistically significant (P>0.05). The combination of two drugs increased Bax protein level (P<0.05). P21protein in each group are raised higher than D group and control group, especially in combination groups, significantly (P<0.05).7. Cell survival fraction was obviously lower after treatment with the combination of SAHA and radiation than that of radiation alone (P<0.05). The cell survival curve of combination groups were to the left compared with radiotherapy groups. The front one was relatively flat and the shoulder area is not obvious. Do of the X-ray groups and the combination groups were2.329and1.213respectivly. The Dq were1.721and0.823respectively. The SFR was1.92.8. Expression of Bax mRNA of radiotherapy groups were higher then the control groups(P<0.05). The expressions of combination groups of Ku70mRNA were were lower then than the radiotherapy groups (P<0.05).
Conclusions
1. SAHA has the synergistic effect with DDP on SiHa cells.2. SAHA can arrest cell cycle and induce apoptosis of SiHa cells with DDP.3. The mechanism might be associated with up-regulating expression of P21and Bax mRNA and protein.4. Low concentrations of SAHA enhanced the radiosensitivity of SiHa cells.6. Up-regulating the expression of Bax and down-regulating the expression of Ku70response to the sensitization enhancement of SAHA to Siha cells.
方法：1、以SAHA0.25、0.5、1、2、4、6μ mol/L和DDP1、2、4、6、8、10μg/mL分成单药组和不同浓度SAHA+DDP联合用药组,另设不加药对照组,作用于体外培养的人宫颈癌SiHa(?)细胞。采用MTT比色法检测各组SiHa细胞的增殖抑制率；流式细胞术检测各组的细胞周期；用AnnexinV-FITC标记药物作用后的细胞,了解其早期凋亡的情况；2、20%IC50SAHA预处理SiHa细胞24h后与不同剂量X射线(0Gy、1Gy、2Gy、4Gy、6Gy、8Gy)联合,利用细胞克隆形成实验检测照射后集落形成率,并计算细胞存活分数；根据单击多靶模型SF=1-(1-e-D/Do。)n拟合生存曲线并计算外推值,平均致死剂量和准阈剂量以及放射增敏比；3、用RT-PCR法和Western blot法分析药物作用及射线照射后宫颈癌细胞中P21、Bax和Ku70的mRNA和蛋白的表达；
结果：1、SAHA(?)单药处理细胞时,各组对SiHa细胞的生长抑制率均比对照组升高(P<0.05)；随着给药时间延长,细胞的生长抑制率逐渐升高(P<0.05)。2、SAHA与DDP联合作用SiHa细胞24h,不同剂量联合组对细胞的抑制率均较单用DDP明显(P<0.05)；与1、2、4ug/ml DDP联合应用时,随SAHA剂量的增大抑制率逐渐增高(P<0.05)；SAHA在剂量浓度为1、2、4μ mol/L时,细胞的抑制率随DDP浓度的增加而升高；联用的效果Q值显示SAHA和相对中低剂量的DDP联合用药表现为协同作用,较高剂量的DDP联合用药为单纯相加作用。3、SAHA1、2、4μ mol/L(S组)分别与DDP1、2、4ug/ml(D组)联合(SD组)作用于SiHa细胞,与对照组比较,S组、D组及SD组G0/G1期比例明显增加,而G2/M+S期细胞比例明显减少,PI明显下降(P<0.05)；与S及D组比较,SD组G0/G1期比例明显增加,而G2/M+S期细胞比例明显减少,PI明显下降(P<0.05)；4、各联合组早期凋亡细胞比例均较单药组明显升高(P<0.05)；在2μ g/ml的DDP作用SiHa细胞24h后,细胞凋亡不明显,但经2μ mol/L SAHA预处理后,细胞凋亡率显著增加,且随着SAHA浓度的增加,凋亡率也增加(P<0.05)。5、Bax mRNA及蛋白在S、D组表达比较微弱,与对照组比较无差异(P>0.05),联合作用后BaxmRNA及蛋白的表达显著高于其他各组(P<0.05)；6、P21mRNA及蛋白在各组的表达均上调,以联合组的表达上调显著,明显高于D组和对照组(P<0.05)。7、SAHA联合照射组的细胞存活分数明显低于单独放疗组,随放疗剂量的增高,细胞存活分数逐渐降低(P<0.05)；利用多靶单击数学模型绘制出细胞辐射存活曲线,可见联合组曲线较单纯照射组左移,且较为平直、“肩区”不明显。单独照射组和联合组平均致死剂量Do分别为2.329、1.213,外推数N分别为2.761、4.770,准阈剂量Dq分别为1.721、0.823。放射增敏比为1.92。8、SAHA组BaxmRNA及蛋白的表达与对照组比较差异无统计学意义(P<0.05)，照射组明显高于对照组(P<0.05),SAHA联合照射组明显高于其它各组(P<0.05)；SAHA(?)关合照射组细胞Ku70mRNA及蛋白的表达明显低于照射组(P<0.05)；
结论：1、SAHA在体外能够抑制人宫颈癌SiHa (?)细胞的生长,抑制作用呈时间剂量依赖性。2、SAHA联合DDP作用SiHa细胞,在体外可以显著诱导细胞凋亡,并使细胞周期阻滞于GO/G1期,二者具有协同作用。3、SAHA联合DDP作用SiHa细胞,能够显著地上调p21、Bax的mRNA及蛋白表达水平,可见促进细胞凋亡及阻断细胞周期可能是SAHA (?)曾强SiHa细胞对DDP敏感性的机制之一。4、小剂量SAHA在体外能够促进SiHa细胞对X-线照射的敏感性。5小剂量SAHA通过增加放射诱导细胞凋亡基因Bax的表达及下调DNA修复基因Ku70的表达,促进了细胞的凋亡,抑制了细胞的修复,从而实现对SiHa(?)细胞的放射增敏作用。
Objective
To observe the sensitizing effects of the HDAC inhibitor suberoylanilide ydroxamic acid (SAHA) combined with DDP or X ray to cervical cancer SiHa cells and the mechanism of sensitization as well through studying the growth inhibition and apoptosis, cell colons formation rate and the result of the radiation sensitive parameters of cerical cancer cells.
Methods
1. SiHa cells were treated with0.25,0.5,1,2,4and6μmol/L of SAHA, and1.2,4,6,8and10μg/mL of DDP, respectivly. SiHa cells were treated with the vary combination dose of the two drugs. The inhibitory rate of SiHa cells were analyzed with MTT; Cell cycle distribution was detected by flow cytometry; Apoptosis of cells was measured by Annexin V-FITC.2. SiHa cells were incubated with SAHA at the concentration of20%IC50for24h and then were exposed to X-ray irradiation (IR)(0,2,4,6,8Gy). Colonies and surviving fraction (SF) of cells were detected by Clonogenic assay, the SF、Do and sensitizing enhancement ratio (SER) of each groups and the cell survival curve was gained by single-hit multi-target model.3. P21, Bax and Ku70's mRNA and protein expression levels were investigated by RT-PCR and Western bolt in SiHa cell. Results
1. SAHA was capable of inhibiting SiHa cells growth comparing with control group (P<0.05); SAHA appears more inhibiting SiHa cells growth effect attending by the increasing dose and time.2. The combined groups inhibited the cell growth obversely than single drug groups after24hours (P<0.05); Inhibition rate increased gradually with SAHA increasing dose combined with DDP; The effect of SAHA combined With DDP showed that low doses of DDP combination is synergy, while higher doses of DDP combination has simple addition effect.3. When1,2,4umol/L of SAHA (S group) combined with the DDP1,2,4ug/ml (D group) respectively, all the groups appear arresting cell at G1/G0phase, while the G2/M+S period cells proportion markedly reduced. PI reduced compared with control group significantly (P<0.05). GO/G1phase ratio increased significantly in SD group, while the G2/M+S period cells proportion markedly reduced. PI reduced significantly compared with the S group and D group (P<0.05).4. SAHA combing with DDP induced more severe apoptosis than separate groups (P<0.05). Apoptosis in2ug/mL DDP group was not obviously, but after pretreatment by2umol/L SAHA, apoptosis rate increased significantly.5. Compared the expression of Bax mRNA with the control group, there was no statistical significance of D, S group(P>0.05), while the expressions of combination groups were higher then other groups(P<0.05); P21expression in each group is raised significantly, especially in combination groups comparing with D group and control group (P<0.05).6. Bax protein expression between SAHA groups and the control group was not statistically significant (P>0.05). The combination of two drugs increased Bax protein level (P<0.05). P21protein in each group are raised higher than D group and control group, especially in combination groups, significantly (P<0.05).7. Cell survival fraction was obviously lower after treatment with the combination of SAHA and radiation than that of radiation alone (P<0.05). The cell survival curve of combination groups were to the left compared with radiotherapy groups. The front one was relatively flat and the shoulder area is not obvious. Do of the X-ray groups and the combination groups were2.329and1.213respectivly. The Dq were1.721and0.823respectively. The SFR was1.92.8. Expression of Bax mRNA of radiotherapy groups were higher then the control groups(P<0.05). The expressions of combination groups of Ku70mRNA were were lower then than the radiotherapy groups (P<0.05).
Conclusions
1. SAHA has the synergistic effect with DDP on SiHa cells.2. SAHA can arrest cell cycle and induce apoptosis of SiHa cells with DDP.3. The mechanism might be associated with up-regulating expression of P21and Bax mRNA and protein.4. Low concentrations of SAHA enhanced the radiosensitivity of SiHa cells.6. Up-regulating the expression of Bax and down-regulating the expression of Ku70response to the sensitization enhancement of SAHA to Siha cells.
引文
[1]Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics,2002, [J] CA Cancer Clin.2005; 55:74-108.
[2]Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents:defining priorities to reduce cancer disparities in different geographic region of the world [J]. J Clin Oncol.2006; 24:2137-2150.
[3]Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics,2009 [J]. CA Cancer J Clin.2009; 59:225-249.
[4]Diaz RC, Montaner B, Perez TR. Prodigiosin induces cell death and morphological changes indicative of apoptosis in gastric cancer cell line HGT-1 [J]. Histol Histopathol,2001,16(2):415-21.
[5]Leonardi A, DeFranchis G, Fregona IA, et al. Effects of cyclosporine A on human conjunctival fibroblasts [J]. Arch Ophthalmol,2001,119(10):1512-7.
[6]Bedoya LM, Sanchez PS, Ahad MJ, et al. Anti-HIV activity of medicinal plant extracts [J]. J Ethnopharmacol 2001,77(1):113-6.
[7]Verdone L, Agricola E, Caserta M, et al. Histone acetylation in gene regulation [J]. Briefings in Functional Genomics and Proteomics,2006,5(3):209-221.
[8]Mann BS, Johnson JR, Cohen MH, et al. FDA approval summary:vorinostat for treatment of advanced primary cutaneous T-cell lymphoma [J]. Oncologist, 2007,2(10):1247-1252.
[9]Marks PA, Richon VM, Miler T, et al. Histone deacetylase inhibitors [J]. Adv Cancer Res,2004,91:137-168.
[10]Luong QT, O'Kelly J, Braunstein GD, et al. Antitumor activity of sub-eroylanilide hydroxamic acid against thyroid cancer cell lines in vitro and in vivo[J]. Clin Cancer Res,2006,12(18):5570-5577.
[11]戴体俊.合并用药的定量分析[J].中国药理学通报,1998,14(5)：479.
[12]曹泽毅.子宫颈癌治疗的变迁和思考[J].现代妇产科进展,2005,14(1)：1-5.
[13]Anton M, Horky M, Kuchtickova S, et al. Immunohistochemical detection of acetylation and phosphorylation of histone H3 in cervical smears [J]. Ceska Gynekol 2004,69(1):3-6.
[14]曹振平,凌斌,冯定庆.去乙酰化酶抑制剂抗肿瘤作用研究进展[J].国际妇产科学杂志,2010,37(4)：267-270.
[15]Muggia FM. Recent updates in the clinical use of platinum compounds for the treatment of gynecologic cancers [J]. Semin Oncol,2004,31 (6 suppl 14):17-24.
[16]张丽杰,武湘云,赵振军,等.顺铂诱导人卵巢癌细胞HO-8910细胞凋亡和P53表达的研究[D].河北医科大学,2002
[17]Lee DY, Hayes JJ, Pruss D, et al. A positive role for histone acetylation in transcription factor access to nucleosomal DNA [J]. Cell,1993,72(1):73.
[18]Kim MS, Blake M, Baek JH, et al. Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA [J]. Cancer Res,2003,63(21): 7291-7300.
[19]Canes D, Chiang GJ, Billmeyer BR, et al. Histone deacetylase inhibitors upregulate plakoglobin expression in bladder carcinoma cells and display antineoplastic activity in vitro and in vivo[J]. hit J Cancer,2005,113(5):841.
[20]Fulda S, Sieverts H, Friesen C et al. The CD95 (APO-1Fas) system mediates drug-induced apoptosis in neuroblastoma cells. [J] Cancer Res.1997; 57(17): 3823-9.
[21]Friesen C, Herrl, Kranuner PH et al. Involvement of the CD95 (APO-1/FAS) receptor/ligand system in drug-induced apoptosis in leukemia cells [J]. Nat Med. 1996:2(5):574-7.
[22]马国栋,张才全,侯俊.HDAC在PPARy途径抑制胃癌SGC-7901细胞侵袭中的作用[J].癌症,2009,28(7)：695-701.
[23]曲巍,王立明,朱有华等.组蛋白去乙酰酶抑制剂MS-275抑制膀胱癌的实验研究[J].中国癌症杂志,2006,25(1)：592-594.
[24]Budillion A, Bruzzese F, Di gennaro E, et al. Multiple-target drugs:inhibitators of heat shock protein 90 and of histone deacetylase [J], Curr Drug Targets:2005, 6(3):337-351
[25]Yin D, Ong JM, Hu J, et al. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor:effects on gene expression and growth of glioma cells in vitro and in vivo[J]. Clin Cancer Res,2007,13(3):1045-1052.
[26]Arundel C, Glicksman A, Leith J. Enhancement of radiation injury in human colon tumor cells by the maturational agent sodium butyrate (NaB) [J]. Radiat Res,1985,104(3):443-448
[27]Biade S, Stobbe CC, Boyd JT, et al.Chemical agents that promote chromatin compaction radiosensitize tumor cells [J]. Int J Radiat Biol,2001,77(10): 1033-1042
[28]Geng L, Cuneo KC, Fu A, et al. Histone deacetylase(HDAC)inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer [J]. Cancer Res,2006,66(23): 11298-11304.
[29]Kim IA, Shin JH, Kim IH, et al. Histone Deacetylase Inhibitor-Mediated Radiosensitization of Human Cancer Cells:Class Differences and the Potential Influence of p53 [J]. Clin Cancer Res,2006,12(3):940-949
[30]Kim JH, Shin JH, Kim IH. Susceptibility and radiosensitization of human glioblastoma cells to trichostatin A, a histone deacetylase inhibitor[J]. Int J Radiat Oncol Biol Phys,2004,59(4):1174-1180
[31]Munshi A, Kurland JF, Nishikawa T, et al.Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity [J]. Clin Cancer Res,2005,11(13):4912-4922.
[32]Karagiannis TC, KN H, El-Osta A. The epigenetic modifier, valproic acid, enhances radiation sensitivity [J]. Epigenetics,2006,1(3):131-137.
[33]Zhang Y, Adachi M, Kawamura R, et al. Bmf contributes to histone deacetylase inhibitor-mediated enhancing effects on apoptosis after ionizing radiation[J]. Apoptosis.2006,11(8):1349-1357.
[34]Ungerstedt JS, Sowa Y, et al. Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors [J]. Proc Natl Acad Sci USA, 2005; 102(3):673-678
[35]Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors:molecular mechanisms of action [J]. Oncogene,2007,26 (37):5541-5552.
[36]胡硕,胡成平.线粒体与细胞凋亡的研究进展.国际呼吸杂志[J].2006,25(6)：561-569.
[37]Wu ZQ, Zhang R, Chao C, et al. Histone deacetylase inhibitor trichostatin A induced caspase-independent apoptosis in human gastric cancer cell[J]. Chin Med J (Engl).2007 Dec 5; 120(23):2112-8.
[38]Shiohara M, Deiry WS, Wada M, et al. Absence of WAF1 mutations in a variety of human malignancies [J]. Blood,1994,84(11):3781-3784.
[39]Zhang C, Richon V, Ni X, et al. Selective induction of apoptosis by deacetylase inhibitor SAHA in cutaneous T-cell lymphoma cells:relevance to mechanism of therapeutic action [J]. J Invest Dermatol,2005,125(5):1045.
[40]Chinnaiyan P, Vallabhaneni G, Armstrong E, et al. Modulation of radiation response by histone deacetylase inhibition[J]. Int J Radiat Oncol Biol Phys, 2005,62(1):223-229.
[41]Zhang Y, Adachi M, Zou H, et al. Histone deacetylase inhibitors enhance phosphorylation of histone H2AX after ionizing radiation[J]. Int J Radiat Oncol Biol Phys,2006,65(3):859-866
[42]Jeggo PA. Risk from low does/does rate radiation:what an understanding of DNA damage response mechaniams can tell us [J]. Health Phys,2009, 97(5):416-425.
[43]Munshi A, Kurland JF, Nishikawa T, et al. Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity [J]. Clin Cancer Res 2005; 11:4912-4922.
[44]Cheng CS, Wang YC, Yang HC, et al. Histone deacetylase inhibitors sensitize prostate cancer cells to agents that produce DNA double-strand breaks by targeting Ku7 Oacetylation [J]. Cancer Res,2007,67(11):5318-5327.
[45]Du ZH, Ma KW, Yang GZ, et al. Mechanism of leukemia cell apoptosis induced by sodium butyrate activating TRAIL pathway[J].Zhong Guo Shi Yan Xue Ye Xue Za Zhi,2009,17 (2):315-318.
[46]Portanova P, Russo T, Pellerito O, et al. The role of oxidative stress in apoptosis induced by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in human colon adenocarcinoma HT-29 cells [J]. Oncology,2008,33 (2):325-331.
[47]Taghiyev AF, Guseva NV, Sturm MT, et al.Trichostatin A (TSA) sensitizes the human prostatic cancer cell line DU145 to death receptor ligands treatment[J]. Cancer Biol Ther,2005,4(4):382-390.
[48]Portanova P, Russo T, Pellerito O, et al. The role of oxidative stress in apoptosis induced by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in human colon adenocarcinoma HT-29 cells [J]. Oncology,2008,33(2):325-331.
[49]Fritsche P, Seidler B, Schuler S, et al. HDAC2 mediates therapeutic resistance of pancreatic cancer cells via the BH3-only protein NOXA [J]. Gut,2009, 58(10):1399-1409.
[50]Yuki H, Fujkmura M, Yamakawa Y, et al.Detection of prognosis after irradiation therapy in stageⅢb uterine cervical cancer [J].Cencer Res,2000,91(1):127-134.
[51]束凯俊,陈传生.细胞凋亡及其相关蛋白Bax在宫颈癌放疗中的价值[J]。江苏医药2005,31(9)：703-704.
[52]Peltonen K, Kiviharju TM, Jarvinen PM, et al.Melanomacell lines are susceptible to histone deacetylase inhibitor TSA provoked cell cycle arrest and apoptosis[J]. Pigment Cell Res.2005 Jun; 18(3):196-202
[53]Roy S, Packman K, Jeffrey R, et al. Histone deacetylase inhibitors Differentially stabilize acetylated p53 and induce cell cycle arrest or apoptosis in prostate cancer cells [J]. Cell Death Differ,2005,12(5):482-91.
[54]ZhaoY, Chaiswing L, Velez JM, et al. p53 translocation to Mitochondria precedes its nuclear translocation and targets Mitochondrial oxidative defense protein-manganese superoxide dismutase[J]. Cancer Res,2005,65 (9):3745-50..
[55]Chen X, Wong P, Radany E, et al. HDAC inhibitor, valproic acid, induces p53-dependent radiosensitization of colon cancer cells. Cancer Biother Radio pharm[J].2009, Dec,24(6):689-699.
[56]夏景光,王菊芳,李文建。组蛋白H2AX的磷酸化及其在放射生物学中的潜在应用[J]。中华放射医学与防护杂志,2005,25(6)：581-584.
[57]Karagiannis T, Harikrishnan K, El-Osta A, etal.The histone deacetylase inhibitor, Trichostatin A, enhances radiation sensitivity and accumulate on of gamma H2AX [J]. Cancer Biol Ther,2005,4(7):787-793.
[58]Munshi A, Tanaka T, Hobbs ML, et al. Vorinostat, a histone deacetylase inhibitor, enhances the response of human tumor cells to ionizing radiation through prolongation of y-H2AX foci. Mol Cancer Ther.2006 Aug;5(8):1967-74
[1]Huang C, Sloan EA, Boerkoel CF. Chromatin remodeling and human disease [J]. Curr Opin Genet Dev,2003,13(3):246-252.
[2]安丽娜,王树人。组蛋白乙酰化/去乙酰化与染色质结构及基因转录调控的关系[J]。国外医学遗传学分册,2005,28(3)：133-137
[3]Loredana V, Eleonora A, et al. Histone acetylation in gene regulation [J]. Briefings in Functional Genomics and Proteomics,2006,5(3):209-221.
[4]Gregory PD, Wagner K, et al. Histone acetylation and chromatin remodeling [J]. Exp Cell Res,2001 265(2):195-202.
[5]Pikaart MJ, Recillas-Targa F, Felsenfeld G. Loss of transcriptional activity of a transgene is accompanied by DNA methylation and histone deacetylation and is prevented by insulators [J].Genes Dev,1998,12(18):2852-2862.
[6]Roth SY, Denu JM, Allis CD. Histone acetyltransferases [J].Amiu Rev Biochem,2001,70:81-120.
[7]Kouzarides T.Chromatin modifications and their function[J]. Cell,2007,128 (4):693-705
[8]Loredana V, Eleonora A, Micaela, et al.Histone acetylation in gene regulation. Briefings in Functional Genomics and Proteomics,2006,5(3):209-221.
[9]Taghiyev AF, Guseva NV, Sturm MT, et al. Trichostatin A(TSA) Sensitizes the human prostatic cancer cell line DU145 to death receptor ligands treatment [J]. Cancer Biol Ther,20054(4):382-390.
[10]Bokelmann I, Mahlknecht U. Valproic acid sensitizes chroniclymphocytic leukemia ceils to apoptosis and restores the balance between pro-and antiapoptotic proteins[J]. MolMed,2008,14(12):20-27.
[11]陈萦桓,房静远,陆娟,等.组蛋白乙酰化对人结肠癌细胞系细胞周期的影响[J].胃肠病学,2002,7(Suppl.)60-61.
[12]曹振平.去乙酰化酶抑制剂抗肿瘤作用研究进展[J].国际妇产科学杂志,2010,37(4)：267-270.
[13]Du ZH, Ma KW, Yang GZ, et al. Mechanism of leukemia cell apoptosis induced by sodium butyrate activating TRAIL pathway [J].Zhong Guo Shi Yan Xue Ye Xue Za Zhi,2009,17(2):315-318.
[14]Taghiyev AF, Guseva NV, Sturm MT, et al. Trichostatin A(TSA) Sensiti zes the human prostatic cancer cell line DU145 to death receptor ligands treatment [J]. Cancer Biol Ther,2005,4(4):382-390.
[15]Bokelmann I, Mahlknecht U. Valproic acid sensitizes chronicly-mphocytic leukemia ceils to apoptosis and restores the balance between pro-and antiapopto-tic proteins[J]. Mol Med,2008,14(12):20-27.
[16]Wu ZQ, Zhang R et al. Histone deacetylase inhibitor trichostatin A induced caspase-independent apoptosis in human gastric cancer cell.Chin Med J (Engl), 2007,120(23):2112-2118.
[17]Zhang C, Richon V, Ni X, et al. Selective induction of apoptosis by deacetylase inhibitor SAHA in cutaneous T-cell lymphoma cells:relevance to mechanism of therapeutic action [J]. J Invest Dermatol,2005,125(5):1045.
[18]Lee DY, Hayes JJ, Pruss D, et al. A positive role for histone acetylation in transcription factor access to nucleosomal DNA [J].Cell,1993,72 (1):73.
[19]Kim MS,Blake M,Baek JH,et al.Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA [J].Cancer Res,2003,63 (21): 7291-7300.
[20]张敏,李彪,张一帆.组蛋白去乙酰化酶抑制剂在抗肿瘤应用中的进展[J]。国际放射医学核医学杂志,2007,31(5)：270-273.
[21]Glaser K B. HDAC inhibitors:clinical update and mechanism-based potent ial[J].Biochem Pharmacol,2007,74(5):659-671.
[22]Bjerling P, Silverstein RA, Thon G, et al. Functional Divergence between histone deacetylases in fission yeast by distinct cellular localization and in vivo specificity[J].Mol Cell Biol,2002,22(7):2170-2181.
[23]Marks PA, Richon VM, et al. Histone deacetylase inhibitors [J]. Adv Cancer Res,2004,91(1):137-168.
[24]Weichert W. HDAC expression and clinical prognosis in human malignancies [J].Cancer Lett,2009 Aug 8; 280(2):168-176.
[25]Marks P A, Dokmanovic M. Histone deacetylase inhibitors:discovery and development as anticancer agents[J].Expert Opin Investig Drugs,2005,14 (12): 1497-1511.
[26]Marks PA, Dokmanovic M.Histone deacetylase inhibitors:discovery and development as anticancer agents [J]. Expert Opin Investig Drugs,2005,14 (12):1497 -1511.
[27]马国栋,等.HDAC在PPARγ途径抑制胃癌SGC-7901细胞侵袭中的作用[J].癌症,2009,28(7)：695-701.
[28]曲巍王,立明朱,有华,等.组蛋白去乙酰化酶抑制剂联合抗癌药物抑制膀胱癌的实验研究[J].实用医药杂志,2008,25(5)：592-594.
[29]邓放,王广义,梁舸.组蛋白去乙酰化酶抑制剂与5-FU合用对肝癌细胞HepG2的影响[J].中国免疫学杂志,2008,24(1)：34-37.
[30]Glaser KB.HDAC inhibitors：clinical update and mechanism based potential [J]. Biochem Pharmacol,2007,74(5):659-671.
[31]李宏,舒艺,陈勇军,等DNMTi与HDACi旦管癌细胞E-cadherin表达和细胞侵袭力的影响[J].中国普外基础与临床杂志,2009,16(1)：44-46.
[32]张嵩,牟晓燕,王红梅,等.5-氮-2’-脱氧胞苷和曲古抑菌素A对子宫内膜腺癌细胞的抑制作用[J].中国肿瘤生物治疗杂志.2008；15(4)：623-30.
[33]杨艳娜,王艳,王星光,等.曲古抑菌素A和紫杉醇对子宫内膜癌Ark2细胞凋亡和线粒体膜电位的影响[J]Chinese Journal of Cancer,2008,27(8) 816-821.
[34]Arundel C, Glicksman A, Leith J. Enhancement of radiation injury in human colon tumor cells by the maturational agent sodium butyrate(NaB) [J]. Radiat Res,1985,104(3):443-448
[35]Biade S, Stobbe C, Boyd J, et al.Chemical agents that promote chromatin compaction radiosensitize tumor cells[J]. Int J Radiat Biol,2001,77 (10):1033-1042.
[36]Geng L, Cuneo KC, Fu A, et al. Histone deacetylase(HDAC)inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer [J].Cancer Res,2006,66 (23):11298-11304.
[37]Kim IA, Shin JH, Kim IH, et al.Histone Deacetylase Inhibitor-Mediated Radiosensitization of Human Cancer Cells:Class Differences and the Potential Influence of p53 [J].Clin Cancer Res,2006,12(3):940-949.
[38]Kim JH, Shin JH, Kim IH. Susceptibility and radiosensitization of human glioblastoma cells to trichostatin A,a histone deacetylase inhibitor. Int J Radiat Oncol Biol Phys[J],2004,59(4):1174-1180.
[39]Munshi A,Kurland JF,Nishikawa T,et al.Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity [J]. Clin Cancer Res,2005,11(13):4912-4922.
[40]Camphausen K,Cerna D,Scott T,et al.Enhancement of in vitro and in vivo tumor cell radiosensitivity by valproic acid.International journal of cancer [J], 2005,114(3):380-386.
[41]Camphausen K,Burgan W,Cerra M,et al.Enhanced radiation-induced cell killing and prolongation of gammaH2AX foci expression by the histone deacetylase inhibitor MS-275[J].Cancer Res,2004,64(1):316-321.
[42]Koniaras K, Cuddihy A R, et al. Inhibition of CHkl-dependent G2 DNA damage checkpoint radiosensitizes p53 mutant human cells[J]. Oncogene,2001, 20:7453.
[43]O live PL, Banh JP, Durand RE. Development of apoptosis and polyploidy in human lymphoblast cells as a function of position in the cell cycle at the time of irradition [J]. Radiat Res,1996,146 (6):595-602.
[44]张孟贤,于世英.宫颈癌细胞周期阻滞和凋亡与放射敏感性的关系[J].中华放 射肿瘤学杂志2002,11(2)：116-117.
[45]Sinclair,W. K, and Morton, R. A. X-ray sensitivity during the cell generation cycle of cultured Chinese hamster cells[J]. Radial Res,29:450-474.
[46]Johnstone RW, Licht JD. Histone deacetylase inhibitors in cancer ther apy:Is transcrip tion the p rimary target[J]. Cancer Cell,2003,4:13-18.
[47]Zhang Y, Jung M, Dritschilo A, et al. Enhancement of radiation sensitivity of human squamous carcinoma cells by histone deacetylase inhibitors[J]. Radiat Res,2004, 1(6):667-674.
[48]Zhang F, Zhang T, et al. Sensitization to gamma-irradiation-induced cell cycle arrest and apoptosis by the histone deacetylase inhibitor trie-hostatin A in non-small cell lung cancer (NSCLC) cells[J]. Cancer Biol Ther.2009 May; 8 (9):823-831.
[49]Flatmark K,Nome RV,et al.Ree AH Radiosensitization of colorectal carcinoma cell lines by histone deacetylase inhibition. Radiat Oncol [J].2006 Aug 3:1:25.
[50]Poplawski T, Stoczynnsk E, Blasiak J. Non-homologous DNA end joining-new proteins, new functions,new mechanisms[J]. Postepy Bioch-em,2009,55 (1): 36-45.
[51]Kim YC, Gerlitz G, et al. Activation of ATM depends on chromatin interactions occurring before induction of DNA damage[J]. Nat Cell Biol.,2009,11(1):92-96.
[52]Gary DK, Gillies M, et al.Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response[J], The Journal of Cell Biology,2003,160 (7):1017-1027.
[53]Munshi A,Kurland JF,et al.Histone deacetylase inhibitors radiosen-sitize human melanoma cells by suppressing DNA repair activity[J]. Clin Cancer Res 2005; 11:4912-4922.
[54]Chinnaiyan P, Vallabhaneni G,et al. Modulation of radiation response by histone deacetylase in-hibition [J]. Int J Radiat Oncol Biol Phys 2005; 62: 223-229.
[55]Karagiannis TC, El-osta A. Modulation of radiation response by histone deacetylase inhibition [J]. Int J Radiat Oncol Biol Phys,2005,62 (1):223-229.
[56]Munshi A,Kurland JF,et al.Histone deacetylase inhibitors radiosen-sitize human melanoma cells by suppressing DNA repair activity [J]. Clin Cancer Res 2005; 11:4912-4922.
[57]Anupama M, John FK,et al.Histone deacetylase inhibitors radiosen-sitize human melanoma cells by suppressing DNA repair activity [J]. Clin Cancer Res, 2005,11:4912-4922.
[58]Cohen HY, Lavu S, et al. Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis[J]. Mol Cell,2004,13 (5):627-638.
[59]Chang CS, Wang YC, et al. Histone deacetylase inhibitors sensitize prostate cancer cells to agents that produce DNA double-strand breaks by targeting Ku70 acetylation [J].Cancer Res,2007,67 (11):5318-5327.
[60]Subramanian C, Opipari AW Jr, et al. Ku70 acetylation mediates neuroblastoma cell death induced by histone deacetylase inhibitors[J]. Proc Natl Acad Sci USA 2005; 102:4842-4847.
[61]Yaneva M, Li H, et al. Non-homologous end joining, but not homologous recombination, enables survival for cells exposed to a hi stone deacetylase inhibitor [J].Nucleic Acids Res 2005; 33:5320-5330.
[62]夏景光,王菊芳,李文建。组蛋白H2AX的磷酸化及其在放射生物学中的潜在应用[J]。中华放射医学与防护杂志,2005,25(6)：581-584.
[63]Chowdhury D, Keogh M c, et al. γ-H2AX dephos-porylation by Protein Phosphatase ZA facilitates DNA doublestrand break repair [J]. Mol Cell,2005, 20(5):801-809.
[64]Rothkamm K, Kruger I, et al. Pathways of DNA double-strand break repair during the mammalian cell cycle[J]. Mol Cell Biol 2003; 23:5706-5715.
[65]Nazarov IB, Smirnova AN, et al. Dephosphorylation of histone gamma-H2AX during repair of DNA double-strand breaks in mammalian cells and its inhibition by calyculin A[J]. Radiat Res 2003; 160:309-317.
[66]MacPhail SH, Banath JP, et al. Expression of phosphorylated histone H2AX in cultured cell lines following exposure to X-rays.[J]. Int J Radiat Biol 2003; 79: 351-358.
[67]Zhang Y, Adachi M, Zou H, et al. Histone deacetylase inhibitors enhance phosphorylation of histone H2AX after ionizing radiation[J]. Int J Radiat Oncol Biol Phys,2006,65 (3):859-866.
[68]Camphausen K, Burgan W, et al. Enhanced radiation-induced cell killing and prolongation of gammaH2AX foci expression by the histone deacetylase inhibitor MS-275[J].Cancer Res,2004,64 (1):316-321.
[69]Munshi A, Kurland JF, et al. Enhanced radiation-induced cell killing and prolongation of gammaH2AX foci expression by the histone deacetylase inhibitor MS-275 [J]. Cancer Res,2004,64(1):316-321.
[70]Karagiannis T, Harikrishnan K, et al. The histone deacetylase inhibitor, Trichostatin A,enhances radiation sensitivity and accumula-tion of gamma H2AX [J]. Cancer Biol Ther,2005,4 (7):787-793.
[71]Insinga A, Monestiroli S, Ronzoni S, et al. Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway[J]. Nat Med,2005,11(1):71-76.
[72]Taghiyev AF, Guseva NV, et al. Trichostatin A (TSA) Sensitizes the human prostatic cancer cell line DU145 to death receptor ligands treatment[J]. Cancer Biol Ther,2005,4(4):382-390.
[73]Zhang Y, Adachi M, et al. Bmf is a possible mediator in histone deacetylase inhibitors FK228 and CBHA-induced apoptosis [J].Cell Death Differ,2006, 13:129-140.
[74]Yu X D, Wang S Y, et al. Apoptosis induced by depsipeptide FK228 coincides with inhibition of survival signaling in lung cancer cells [J]. Cancer J,2007, 13(2):105-113.
[75]Subramanian C, Opipari AW Jr, et al. Ku70 acetylation Mediates neuroblastoma cell death induced by histone deacetylase inhibitors [J]. Proc Natl Acad Sci USA,2005,102(13):4842-4847.
[76]Zhang Y, Adachi M, et al. Bmf contributes to histone deacetylase inhibitor-mediated enhancing effects on apoptosis after ionizing radiation [J]. Apoptosis.2006 Aug; 11(8):1349-1357.
[77]Zhang F, Zhang T, et al. Sensitization to gamma-irradiation-induced cell cycle arrest and apoptosis by the histone deacetylase inhibitor trichostatin A in non-small cell lung cancer (NSCLC) cells [J]. Cancer Biol Ther,2009 May; 8(9):823-831.
[78]Clemens A, Schmitt E M, et al.Apoptosis and Therapy [J]. Pathol,1999, 187:127-129.
[79]Smith ML, Chen IT, et al.Interaction of the p53-regulated protein GADD45 with proliferating cell nuclear antigen [J]. Science,1994,266 (5189):1376-1380.
[80]Chang EH, Jang YJ, et a 1. Restoration of the G1 checkpoint and the apoptotic pathway mediated by wild-type p53 sensitizes squamous cell carcinoma of the head and neck to radiotherapy [J]. Arch Otolaryngol Head Neck Surg,1997,123 (5):507-512.
[81]Quick QA, Gewirtz DA. An accelerated senescence response to radiation in wild-type p53 glioblastoma multiform cells [J]. Neuro surg,2006 Jul; 105 (1): 111-118.
[82]Strasser A, Harris AW, et al. DNA damage can induce apoptosis in proliferating lymphoid cells via p53-independent mechanisms inhibitable by Bcl-2 [J]. Cell,1994,79(2):329-339.
[83]An W, Kim J, et al. Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53 [J]. Cell,2004,17(6):735-748.
[84]Juan LJ, Shia WJ, et al. Histone deacetylases specifically down-reg ulate p53-dependent gene activation [J]. Biol Chem,2000,275 (27):20436-20443.
[85]Luo J,Su F, Chen D, et al. Deacetylation of p53 modulates its effect on cell growth and apoptosis [J]. Nature,2000,408(6810):377-381.
[86]In Ah Kim, Jin Hee Shin, et al. Histone Deacetylase Inhibitor-Media ted Radiosensitization of Human Cancer Cells:Class Differences and the Potential Influence of p53 [J]. Clin Cancer Res 2006; 12:940-949.
[87]Cang SD, Ma YH, Liu DL. New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer [J]. J Hematol Oncol,2009,1(2):22.
[88]M Richon,Y Webb,R Mefger, et al.Second generation hybridpolar compounds are potent inducer of transformed cell differentiation [J]. Proc Natl Acad Sci USA,1996;93;5705-5709.
[89]Uvic M,Vu J.Vorinostat:a new oral histone deacetylase inhibitor approved for cutaneous T-cell lymphoma[J].Expert Opin Investig Drugs,2007,16 (7):1111-1120.
[90]Richardson P, Schlossman RL, Mitsiades CS. Phase I clinical trial of oral administration of the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) in patients with relapsed/refra-ctory multiple myeloma(MM) [J]. Blood (ASH Annual Meeting Abstracts),2004,104: Abstract 1503.
[91]Bhupinder SM,John RJ,Martin HC,et al.FDA approval summary:vorinostat for treatment of advanced primary cutaneous T-cell lymphoma [J]. The Onco logist,2007,2(10):1247-1252.
[92]Canes D, Chiang GJ, Billmeyer BR, et al. Histone deacetylase inhibitors upregulate plakoglobin expression in bladder carcinoma cells and display antineoplastic activity in vitro and in vivo [J]. IntJ Cancer,2005,113 (5):841.
[2]Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents:defining priorities to reduce cancer disparities in different geographic region of the world [J]. J Clin Oncol.2006; 24:2137-2150.
[3]Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics,2009 [J]. CA Cancer J Clin.2009; 59:225-249.
[4]Diaz RC, Montaner B, Perez TR. Prodigiosin induces cell death and morphological changes indicative of apoptosis in gastric cancer cell line HGT-1 [J]. Histol Histopathol,2001,16(2):415-21.
[5]Leonardi A, DeFranchis G, Fregona IA, et al. Effects of cyclosporine A on human conjunctival fibroblasts [J]. Arch Ophthalmol,2001,119(10):1512-7.
[6]Bedoya LM, Sanchez PS, Ahad MJ, et al. Anti-HIV activity of medicinal plant extracts [J]. J Ethnopharmacol 2001,77(1):113-6.
[7]Verdone L, Agricola E, Caserta M, et al. Histone acetylation in gene regulation [J]. Briefings in Functional Genomics and Proteomics,2006,5(3):209-221.
[8]Mann BS, Johnson JR, Cohen MH, et al. FDA approval summary:vorinostat for treatment of advanced primary cutaneous T-cell lymphoma [J]. Oncologist, 2007,2(10):1247-1252.
[9]Marks PA, Richon VM, Miler T, et al. Histone deacetylase inhibitors [J]. Adv Cancer Res,2004,91:137-168.
[10]Luong QT, O'Kelly J, Braunstein GD, et al. Antitumor activity of sub-eroylanilide hydroxamic acid against thyroid cancer cell lines in vitro and in vivo[J]. Clin Cancer Res,2006,12(18):5570-5577.
[11]戴体俊.合并用药的定量分析[J].中国药理学通报,1998,14(5)：479.
[12]曹泽毅.子宫颈癌治疗的变迁和思考[J].现代妇产科进展,2005,14(1)：1-5.
[13]Anton M, Horky M, Kuchtickova S, et al. Immunohistochemical detection of acetylation and phosphorylation of histone H3 in cervical smears [J]. Ceska Gynekol 2004,69(1):3-6.
[14]曹振平,凌斌,冯定庆.去乙酰化酶抑制剂抗肿瘤作用研究进展[J].国际妇产科学杂志,2010,37(4)：267-270.
[15]Muggia FM. Recent updates in the clinical use of platinum compounds for the treatment of gynecologic cancers [J]. Semin Oncol,2004,31 (6 suppl 14):17-24.
[16]张丽杰,武湘云,赵振军,等.顺铂诱导人卵巢癌细胞HO-8910细胞凋亡和P53表达的研究[D].河北医科大学,2002
[17]Lee DY, Hayes JJ, Pruss D, et al. A positive role for histone acetylation in transcription factor access to nucleosomal DNA [J]. Cell,1993,72(1):73.
[18]Kim MS, Blake M, Baek JH, et al. Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA [J]. Cancer Res,2003,63(21): 7291-7300.
[19]Canes D, Chiang GJ, Billmeyer BR, et al. Histone deacetylase inhibitors upregulate plakoglobin expression in bladder carcinoma cells and display antineoplastic activity in vitro and in vivo[J]. hit J Cancer,2005,113(5):841.
[20]Fulda S, Sieverts H, Friesen C et al. The CD95 (APO-1Fas) system mediates drug-induced apoptosis in neuroblastoma cells. [J] Cancer Res.1997; 57(17): 3823-9.
[21]Friesen C, Herrl, Kranuner PH et al. Involvement of the CD95 (APO-1/FAS) receptor/ligand system in drug-induced apoptosis in leukemia cells [J]. Nat Med. 1996:2(5):574-7.
[22]马国栋,张才全,侯俊.HDAC在PPARy途径抑制胃癌SGC-7901细胞侵袭中的作用[J].癌症,2009,28(7)：695-701.
[23]曲巍,王立明,朱有华等.组蛋白去乙酰酶抑制剂MS-275抑制膀胱癌的实验研究[J].中国癌症杂志,2006,25(1)：592-594.
[24]Budillion A, Bruzzese F, Di gennaro E, et al. Multiple-target drugs:inhibitators of heat shock protein 90 and of histone deacetylase [J], Curr Drug Targets:2005, 6(3):337-351
[25]Yin D, Ong JM, Hu J, et al. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor:effects on gene expression and growth of glioma cells in vitro and in vivo[J]. Clin Cancer Res,2007,13(3):1045-1052.
[26]Arundel C, Glicksman A, Leith J. Enhancement of radiation injury in human colon tumor cells by the maturational agent sodium butyrate (NaB) [J]. Radiat Res,1985,104(3):443-448
[27]Biade S, Stobbe CC, Boyd JT, et al.Chemical agents that promote chromatin compaction radiosensitize tumor cells [J]. Int J Radiat Biol,2001,77(10): 1033-1042
[28]Geng L, Cuneo KC, Fu A, et al. Histone deacetylase(HDAC)inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer [J]. Cancer Res,2006,66(23): 11298-11304.
[29]Kim IA, Shin JH, Kim IH, et al. Histone Deacetylase Inhibitor-Mediated Radiosensitization of Human Cancer Cells:Class Differences and the Potential Influence of p53 [J]. Clin Cancer Res,2006,12(3):940-949
[30]Kim JH, Shin JH, Kim IH. Susceptibility and radiosensitization of human glioblastoma cells to trichostatin A, a histone deacetylase inhibitor[J]. Int J Radiat Oncol Biol Phys,2004,59(4):1174-1180
[31]Munshi A, Kurland JF, Nishikawa T, et al.Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity [J]. Clin Cancer Res,2005,11(13):4912-4922.
[32]Karagiannis TC, KN H, El-Osta A. The epigenetic modifier, valproic acid, enhances radiation sensitivity [J]. Epigenetics,2006,1(3):131-137.
[33]Zhang Y, Adachi M, Kawamura R, et al. Bmf contributes to histone deacetylase inhibitor-mediated enhancing effects on apoptosis after ionizing radiation[J]. Apoptosis.2006,11(8):1349-1357.
[34]Ungerstedt JS, Sowa Y, et al. Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors [J]. Proc Natl Acad Sci USA, 2005; 102(3):673-678
[35]Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors:molecular mechanisms of action [J]. Oncogene,2007,26 (37):5541-5552.
[36]胡硕,胡成平.线粒体与细胞凋亡的研究进展.国际呼吸杂志[J].2006,25(6)：561-569.
[37]Wu ZQ, Zhang R, Chao C, et al. Histone deacetylase inhibitor trichostatin A induced caspase-independent apoptosis in human gastric cancer cell[J]. Chin Med J (Engl).2007 Dec 5; 120(23):2112-8.
[38]Shiohara M, Deiry WS, Wada M, et al. Absence of WAF1 mutations in a variety of human malignancies [J]. Blood,1994,84(11):3781-3784.
[39]Zhang C, Richon V, Ni X, et al. Selective induction of apoptosis by deacetylase inhibitor SAHA in cutaneous T-cell lymphoma cells:relevance to mechanism of therapeutic action [J]. J Invest Dermatol,2005,125(5):1045.
[40]Chinnaiyan P, Vallabhaneni G, Armstrong E, et al. Modulation of radiation response by histone deacetylase inhibition[J]. Int J Radiat Oncol Biol Phys, 2005,62(1):223-229.
[41]Zhang Y, Adachi M, Zou H, et al. Histone deacetylase inhibitors enhance phosphorylation of histone H2AX after ionizing radiation[J]. Int J Radiat Oncol Biol Phys,2006,65(3):859-866
[42]Jeggo PA. Risk from low does/does rate radiation:what an understanding of DNA damage response mechaniams can tell us [J]. Health Phys,2009, 97(5):416-425.
[43]Munshi A, Kurland JF, Nishikawa T, et al. Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity [J]. Clin Cancer Res 2005; 11:4912-4922.
[44]Cheng CS, Wang YC, Yang HC, et al. Histone deacetylase inhibitors sensitize prostate cancer cells to agents that produce DNA double-strand breaks by targeting Ku7 Oacetylation [J]. Cancer Res,2007,67(11):5318-5327.
[45]Du ZH, Ma KW, Yang GZ, et al. Mechanism of leukemia cell apoptosis induced by sodium butyrate activating TRAIL pathway[J].Zhong Guo Shi Yan Xue Ye Xue Za Zhi,2009,17 (2):315-318.
[46]Portanova P, Russo T, Pellerito O, et al. The role of oxidative stress in apoptosis induced by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in human colon adenocarcinoma HT-29 cells [J]. Oncology,2008,33 (2):325-331.
[47]Taghiyev AF, Guseva NV, Sturm MT, et al.Trichostatin A (TSA) sensitizes the human prostatic cancer cell line DU145 to death receptor ligands treatment[J]. Cancer Biol Ther,2005,4(4):382-390.
[48]Portanova P, Russo T, Pellerito O, et al. The role of oxidative stress in apoptosis induced by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in human colon adenocarcinoma HT-29 cells [J]. Oncology,2008,33(2):325-331.
[49]Fritsche P, Seidler B, Schuler S, et al. HDAC2 mediates therapeutic resistance of pancreatic cancer cells via the BH3-only protein NOXA [J]. Gut,2009, 58(10):1399-1409.
[50]Yuki H, Fujkmura M, Yamakawa Y, et al.Detection of prognosis after irradiation therapy in stageⅢb uterine cervical cancer [J].Cencer Res,2000,91(1):127-134.
[51]束凯俊,陈传生.细胞凋亡及其相关蛋白Bax在宫颈癌放疗中的价值[J]。江苏医药2005,31(9)：703-704.
[52]Peltonen K, Kiviharju TM, Jarvinen PM, et al.Melanomacell lines are susceptible to histone deacetylase inhibitor TSA provoked cell cycle arrest and apoptosis[J]. Pigment Cell Res.2005 Jun; 18(3):196-202
[53]Roy S, Packman K, Jeffrey R, et al. Histone deacetylase inhibitors Differentially stabilize acetylated p53 and induce cell cycle arrest or apoptosis in prostate cancer cells [J]. Cell Death Differ,2005,12(5):482-91.
[54]ZhaoY, Chaiswing L, Velez JM, et al. p53 translocation to Mitochondria precedes its nuclear translocation and targets Mitochondrial oxidative defense protein-manganese superoxide dismutase[J]. Cancer Res,2005,65 (9):3745-50..
[55]Chen X, Wong P, Radany E, et al. HDAC inhibitor, valproic acid, induces p53-dependent radiosensitization of colon cancer cells. Cancer Biother Radio pharm[J].2009, Dec,24(6):689-699.
[56]夏景光,王菊芳,李文建。组蛋白H2AX的磷酸化及其在放射生物学中的潜在应用[J]。中华放射医学与防护杂志,2005,25(6)：581-584.
[57]Karagiannis T, Harikrishnan K, El-Osta A, etal.The histone deacetylase inhibitor, Trichostatin A, enhances radiation sensitivity and accumulate on of gamma H2AX [J]. Cancer Biol Ther,2005,4(7):787-793.
[58]Munshi A, Tanaka T, Hobbs ML, et al. Vorinostat, a histone deacetylase inhibitor, enhances the response of human tumor cells to ionizing radiation through prolongation of y-H2AX foci. Mol Cancer Ther.2006 Aug;5(8):1967-74
[1]Huang C, Sloan EA, Boerkoel CF. Chromatin remodeling and human disease [J]. Curr Opin Genet Dev,2003,13(3):246-252.
[2]安丽娜,王树人。组蛋白乙酰化/去乙酰化与染色质结构及基因转录调控的关系[J]。国外医学遗传学分册,2005,28(3)：133-137
[3]Loredana V, Eleonora A, et al. Histone acetylation in gene regulation [J]. Briefings in Functional Genomics and Proteomics,2006,5(3):209-221.
[4]Gregory PD, Wagner K, et al. Histone acetylation and chromatin remodeling [J]. Exp Cell Res,2001 265(2):195-202.
[5]Pikaart MJ, Recillas-Targa F, Felsenfeld G. Loss of transcriptional activity of a transgene is accompanied by DNA methylation and histone deacetylation and is prevented by insulators [J].Genes Dev,1998,12(18):2852-2862.
[6]Roth SY, Denu JM, Allis CD. Histone acetyltransferases [J].Amiu Rev Biochem,2001,70:81-120.
[7]Kouzarides T.Chromatin modifications and their function[J]. Cell,2007,128 (4):693-705
[8]Loredana V, Eleonora A, Micaela, et al.Histone acetylation in gene regulation. Briefings in Functional Genomics and Proteomics,2006,5(3):209-221.
[9]Taghiyev AF, Guseva NV, Sturm MT, et al. Trichostatin A(TSA) Sensitizes the human prostatic cancer cell line DU145 to death receptor ligands treatment [J]. Cancer Biol Ther,20054(4):382-390.
[10]Bokelmann I, Mahlknecht U. Valproic acid sensitizes chroniclymphocytic leukemia ceils to apoptosis and restores the balance between pro-and antiapoptotic proteins[J]. MolMed,2008,14(12):20-27.
[11]陈萦桓,房静远,陆娟,等.组蛋白乙酰化对人结肠癌细胞系细胞周期的影响[J].胃肠病学,2002,7(Suppl.)60-61.
[12]曹振平.去乙酰化酶抑制剂抗肿瘤作用研究进展[J].国际妇产科学杂志,2010,37(4)：267-270.
[13]Du ZH, Ma KW, Yang GZ, et al. Mechanism of leukemia cell apoptosis induced by sodium butyrate activating TRAIL pathway [J].Zhong Guo Shi Yan Xue Ye Xue Za Zhi,2009,17(2):315-318.
[14]Taghiyev AF, Guseva NV, Sturm MT, et al. Trichostatin A(TSA) Sensiti zes the human prostatic cancer cell line DU145 to death receptor ligands treatment [J]. Cancer Biol Ther,2005,4(4):382-390.
[15]Bokelmann I, Mahlknecht U. Valproic acid sensitizes chronicly-mphocytic leukemia ceils to apoptosis and restores the balance between pro-and antiapopto-tic proteins[J]. Mol Med,2008,14(12):20-27.
[16]Wu ZQ, Zhang R et al. Histone deacetylase inhibitor trichostatin A induced caspase-independent apoptosis in human gastric cancer cell.Chin Med J (Engl), 2007,120(23):2112-2118.
[17]Zhang C, Richon V, Ni X, et al. Selective induction of apoptosis by deacetylase inhibitor SAHA in cutaneous T-cell lymphoma cells:relevance to mechanism of therapeutic action [J]. J Invest Dermatol,2005,125(5):1045.
[18]Lee DY, Hayes JJ, Pruss D, et al. A positive role for histone acetylation in transcription factor access to nucleosomal DNA [J].Cell,1993,72 (1):73.
[19]Kim MS,Blake M,Baek JH,et al.Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA [J].Cancer Res,2003,63 (21): 7291-7300.
[20]张敏,李彪,张一帆.组蛋白去乙酰化酶抑制剂在抗肿瘤应用中的进展[J]。国际放射医学核医学杂志,2007,31(5)：270-273.
[21]Glaser K B. HDAC inhibitors:clinical update and mechanism-based potent ial[J].Biochem Pharmacol,2007,74(5):659-671.
[22]Bjerling P, Silverstein RA, Thon G, et al. Functional Divergence between histone deacetylases in fission yeast by distinct cellular localization and in vivo specificity[J].Mol Cell Biol,2002,22(7):2170-2181.
[23]Marks PA, Richon VM, et al. Histone deacetylase inhibitors [J]. Adv Cancer Res,2004,91(1):137-168.
[24]Weichert W. HDAC expression and clinical prognosis in human malignancies [J].Cancer Lett,2009 Aug 8; 280(2):168-176.
[25]Marks P A, Dokmanovic M. Histone deacetylase inhibitors:discovery and development as anticancer agents[J].Expert Opin Investig Drugs,2005,14 (12): 1497-1511.
[26]Marks PA, Dokmanovic M.Histone deacetylase inhibitors:discovery and development as anticancer agents [J]. Expert Opin Investig Drugs,2005,14 (12):1497 -1511.
[27]马国栋,等.HDAC在PPARγ途径抑制胃癌SGC-7901细胞侵袭中的作用[J].癌症,2009,28(7)：695-701.
[28]曲巍王,立明朱,有华,等.组蛋白去乙酰化酶抑制剂联合抗癌药物抑制膀胱癌的实验研究[J].实用医药杂志,2008,25(5)：592-594.
[29]邓放,王广义,梁舸.组蛋白去乙酰化酶抑制剂与5-FU合用对肝癌细胞HepG2的影响[J].中国免疫学杂志,2008,24(1)：34-37.
[30]Glaser KB.HDAC inhibitors：clinical update and mechanism based potential [J]. Biochem Pharmacol,2007,74(5):659-671.
[31]李宏,舒艺,陈勇军,等DNMTi与HDACi旦管癌细胞E-cadherin表达和细胞侵袭力的影响[J].中国普外基础与临床杂志,2009,16(1)：44-46.
[32]张嵩,牟晓燕,王红梅,等.5-氮-2’-脱氧胞苷和曲古抑菌素A对子宫内膜腺癌细胞的抑制作用[J].中国肿瘤生物治疗杂志.2008；15(4)：623-30.
[33]杨艳娜,王艳,王星光,等.曲古抑菌素A和紫杉醇对子宫内膜癌Ark2细胞凋亡和线粒体膜电位的影响[J]Chinese Journal of Cancer,2008,27(8) 816-821.
[34]Arundel C, Glicksman A, Leith J. Enhancement of radiation injury in human colon tumor cells by the maturational agent sodium butyrate(NaB) [J]. Radiat Res,1985,104(3):443-448
[35]Biade S, Stobbe C, Boyd J, et al.Chemical agents that promote chromatin compaction radiosensitize tumor cells[J]. Int J Radiat Biol,2001,77 (10):1033-1042.
[36]Geng L, Cuneo KC, Fu A, et al. Histone deacetylase(HDAC)inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer [J].Cancer Res,2006,66 (23):11298-11304.
[37]Kim IA, Shin JH, Kim IH, et al.Histone Deacetylase Inhibitor-Mediated Radiosensitization of Human Cancer Cells:Class Differences and the Potential Influence of p53 [J].Clin Cancer Res,2006,12(3):940-949.
[38]Kim JH, Shin JH, Kim IH. Susceptibility and radiosensitization of human glioblastoma cells to trichostatin A,a histone deacetylase inhibitor. Int J Radiat Oncol Biol Phys[J],2004,59(4):1174-1180.
[39]Munshi A,Kurland JF,Nishikawa T,et al.Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity [J]. Clin Cancer Res,2005,11(13):4912-4922.
[40]Camphausen K,Cerna D,Scott T,et al.Enhancement of in vitro and in vivo tumor cell radiosensitivity by valproic acid.International journal of cancer [J], 2005,114(3):380-386.
[41]Camphausen K,Burgan W,Cerra M,et al.Enhanced radiation-induced cell killing and prolongation of gammaH2AX foci expression by the histone deacetylase inhibitor MS-275[J].Cancer Res,2004,64(1):316-321.
[42]Koniaras K, Cuddihy A R, et al. Inhibition of CHkl-dependent G2 DNA damage checkpoint radiosensitizes p53 mutant human cells[J]. Oncogene,2001, 20:7453.
[43]O live PL, Banh JP, Durand RE. Development of apoptosis and polyploidy in human lymphoblast cells as a function of position in the cell cycle at the time of irradition [J]. Radiat Res,1996,146 (6):595-602.
[44]张孟贤,于世英.宫颈癌细胞周期阻滞和凋亡与放射敏感性的关系[J].中华放 射肿瘤学杂志2002,11(2)：116-117.
[45]Sinclair,W. K, and Morton, R. A. X-ray sensitivity during the cell generation cycle of cultured Chinese hamster cells[J]. Radial Res,29:450-474.
[46]Johnstone RW, Licht JD. Histone deacetylase inhibitors in cancer ther apy:Is transcrip tion the p rimary target[J]. Cancer Cell,2003,4:13-18.
[47]Zhang Y, Jung M, Dritschilo A, et al. Enhancement of radiation sensitivity of human squamous carcinoma cells by histone deacetylase inhibitors[J]. Radiat Res,2004, 1(6):667-674.
[48]Zhang F, Zhang T, et al. Sensitization to gamma-irradiation-induced cell cycle arrest and apoptosis by the histone deacetylase inhibitor trie-hostatin A in non-small cell lung cancer (NSCLC) cells[J]. Cancer Biol Ther.2009 May; 8 (9):823-831.
[49]Flatmark K,Nome RV,et al.Ree AH Radiosensitization of colorectal carcinoma cell lines by histone deacetylase inhibition. Radiat Oncol [J].2006 Aug 3:1:25.
[50]Poplawski T, Stoczynnsk E, Blasiak J. Non-homologous DNA end joining-new proteins, new functions,new mechanisms[J]. Postepy Bioch-em,2009,55 (1): 36-45.
[51]Kim YC, Gerlitz G, et al. Activation of ATM depends on chromatin interactions occurring before induction of DNA damage[J]. Nat Cell Biol.,2009,11(1):92-96.
[52]Gary DK, Gillies M, et al.Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response[J], The Journal of Cell Biology,2003,160 (7):1017-1027.
[53]Munshi A,Kurland JF,et al.Histone deacetylase inhibitors radiosen-sitize human melanoma cells by suppressing DNA repair activity[J]. Clin Cancer Res 2005; 11:4912-4922.
[54]Chinnaiyan P, Vallabhaneni G,et al. Modulation of radiation response by histone deacetylase in-hibition [J]. Int J Radiat Oncol Biol Phys 2005; 62: 223-229.
[55]Karagiannis TC, El-osta A. Modulation of radiation response by histone deacetylase inhibition [J]. Int J Radiat Oncol Biol Phys,2005,62 (1):223-229.
[56]Munshi A,Kurland JF,et al.Histone deacetylase inhibitors radiosen-sitize human melanoma cells by suppressing DNA repair activity [J]. Clin Cancer Res 2005; 11:4912-4922.
[57]Anupama M, John FK,et al.Histone deacetylase inhibitors radiosen-sitize human melanoma cells by suppressing DNA repair activity [J]. Clin Cancer Res, 2005,11:4912-4922.
[58]Cohen HY, Lavu S, et al. Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis[J]. Mol Cell,2004,13 (5):627-638.
[59]Chang CS, Wang YC, et al. Histone deacetylase inhibitors sensitize prostate cancer cells to agents that produce DNA double-strand breaks by targeting Ku70 acetylation [J].Cancer Res,2007,67 (11):5318-5327.
[60]Subramanian C, Opipari AW Jr, et al. Ku70 acetylation mediates neuroblastoma cell death induced by histone deacetylase inhibitors[J]. Proc Natl Acad Sci USA 2005; 102:4842-4847.
[61]Yaneva M, Li H, et al. Non-homologous end joining, but not homologous recombination, enables survival for cells exposed to a hi stone deacetylase inhibitor [J].Nucleic Acids Res 2005; 33:5320-5330.
[62]夏景光,王菊芳,李文建。组蛋白H2AX的磷酸化及其在放射生物学中的潜在应用[J]。中华放射医学与防护杂志,2005,25(6)：581-584.
[63]Chowdhury D, Keogh M c, et al. γ-H2AX dephos-porylation by Protein Phosphatase ZA facilitates DNA doublestrand break repair [J]. Mol Cell,2005, 20(5):801-809.
[64]Rothkamm K, Kruger I, et al. Pathways of DNA double-strand break repair during the mammalian cell cycle[J]. Mol Cell Biol 2003; 23:5706-5715.
[65]Nazarov IB, Smirnova AN, et al. Dephosphorylation of histone gamma-H2AX during repair of DNA double-strand breaks in mammalian cells and its inhibition by calyculin A[J]. Radiat Res 2003; 160:309-317.
[66]MacPhail SH, Banath JP, et al. Expression of phosphorylated histone H2AX in cultured cell lines following exposure to X-rays.[J]. Int J Radiat Biol 2003; 79: 351-358.
[67]Zhang Y, Adachi M, Zou H, et al. Histone deacetylase inhibitors enhance phosphorylation of histone H2AX after ionizing radiation[J]. Int J Radiat Oncol Biol Phys,2006,65 (3):859-866.
[68]Camphausen K, Burgan W, et al. Enhanced radiation-induced cell killing and prolongation of gammaH2AX foci expression by the histone deacetylase inhibitor MS-275[J].Cancer Res,2004,64 (1):316-321.
[69]Munshi A, Kurland JF, et al. Enhanced radiation-induced cell killing and prolongation of gammaH2AX foci expression by the histone deacetylase inhibitor MS-275 [J]. Cancer Res,2004,64(1):316-321.
[70]Karagiannis T, Harikrishnan K, et al. The histone deacetylase inhibitor, Trichostatin A,enhances radiation sensitivity and accumula-tion of gamma H2AX [J]. Cancer Biol Ther,2005,4 (7):787-793.
[71]Insinga A, Monestiroli S, Ronzoni S, et al. Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway[J]. Nat Med,2005,11(1):71-76.
[72]Taghiyev AF, Guseva NV, et al. Trichostatin A (TSA) Sensitizes the human prostatic cancer cell line DU145 to death receptor ligands treatment[J]. Cancer Biol Ther,2005,4(4):382-390.
[73]Zhang Y, Adachi M, et al. Bmf is a possible mediator in histone deacetylase inhibitors FK228 and CBHA-induced apoptosis [J].Cell Death Differ,2006, 13:129-140.
[74]Yu X D, Wang S Y, et al. Apoptosis induced by depsipeptide FK228 coincides with inhibition of survival signaling in lung cancer cells [J]. Cancer J,2007, 13(2):105-113.
[75]Subramanian C, Opipari AW Jr, et al. Ku70 acetylation Mediates neuroblastoma cell death induced by histone deacetylase inhibitors [J]. Proc Natl Acad Sci USA,2005,102(13):4842-4847.
[76]Zhang Y, Adachi M, et al. Bmf contributes to histone deacetylase inhibitor-mediated enhancing effects on apoptosis after ionizing radiation [J]. Apoptosis.2006 Aug; 11(8):1349-1357.
[77]Zhang F, Zhang T, et al. Sensitization to gamma-irradiation-induced cell cycle arrest and apoptosis by the histone deacetylase inhibitor trichostatin A in non-small cell lung cancer (NSCLC) cells [J]. Cancer Biol Ther,2009 May; 8(9):823-831.
[78]Clemens A, Schmitt E M, et al.Apoptosis and Therapy [J]. Pathol,1999, 187:127-129.
[79]Smith ML, Chen IT, et al.Interaction of the p53-regulated protein GADD45 with proliferating cell nuclear antigen [J]. Science,1994,266 (5189):1376-1380.
[80]Chang EH, Jang YJ, et a 1. Restoration of the G1 checkpoint and the apoptotic pathway mediated by wild-type p53 sensitizes squamous cell carcinoma of the head and neck to radiotherapy [J]. Arch Otolaryngol Head Neck Surg,1997,123 (5):507-512.
[81]Quick QA, Gewirtz DA. An accelerated senescence response to radiation in wild-type p53 glioblastoma multiform cells [J]. Neuro surg,2006 Jul; 105 (1): 111-118.
[82]Strasser A, Harris AW, et al. DNA damage can induce apoptosis in proliferating lymphoid cells via p53-independent mechanisms inhibitable by Bcl-2 [J]. Cell,1994,79(2):329-339.
[83]An W, Kim J, et al. Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53 [J]. Cell,2004,17(6):735-748.
[84]Juan LJ, Shia WJ, et al. Histone deacetylases specifically down-reg ulate p53-dependent gene activation [J]. Biol Chem,2000,275 (27):20436-20443.
[85]Luo J,Su F, Chen D, et al. Deacetylation of p53 modulates its effect on cell growth and apoptosis [J]. Nature,2000,408(6810):377-381.
[86]In Ah Kim, Jin Hee Shin, et al. Histone Deacetylase Inhibitor-Media ted Radiosensitization of Human Cancer Cells:Class Differences and the Potential Influence of p53 [J]. Clin Cancer Res 2006; 12:940-949.
[87]Cang SD, Ma YH, Liu DL. New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer [J]. J Hematol Oncol,2009,1(2):22.
[88]M Richon,Y Webb,R Mefger, et al.Second generation hybridpolar compounds are potent inducer of transformed cell differentiation [J]. Proc Natl Acad Sci USA,1996;93;5705-5709.
[89]Uvic M,Vu J.Vorinostat:a new oral histone deacetylase inhibitor approved for cutaneous T-cell lymphoma[J].Expert Opin Investig Drugs,2007,16 (7):1111-1120.
[90]Richardson P, Schlossman RL, Mitsiades CS. Phase I clinical trial of oral administration of the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) in patients with relapsed/refra-ctory multiple myeloma(MM) [J]. Blood (ASH Annual Meeting Abstracts),2004,104: Abstract 1503.
[91]Bhupinder SM,John RJ,Martin HC,et al.FDA approval summary:vorinostat for treatment of advanced primary cutaneous T-cell lymphoma [J]. The Onco logist,2007,2(10):1247-1252.
[92]Canes D, Chiang GJ, Billmeyer BR, et al. Histone deacetylase inhibitors upregulate plakoglobin expression in bladder carcinoma cells and display antineoplastic activity in vitro and in vivo [J]. IntJ Cancer,2005,113 (5):841.