白花丹素对膀胱癌细胞增殖、迁移、侵袭能力的影响及其作用机制
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摘要
目的：研究白花丹素对膀胱癌的生长抑制和诱导细胞凋亡的作用。方法：用1-20umol/L白花丹素干预膀胱癌细胞24-72小时后,用MTT法检测药物对细胞生长的抑制率。用克隆形成实验来检查细胞增殖能力。用AO/EB染色、Hoechst33258染色、Annexin V-FITC/PI双标FCM法检测细胞凋亡。结果：白花丹素以时间和剂量依赖方式抑制T24细胞的增殖。在给与1-20 umol/L白花丹素干预细胞24后,细胞增殖率下降了1.7%-88.1%。在给与1-3umol/L白花丹素处理后,细胞克隆形成率明显下降。2.5-10 umol/L白花丹素干预细胞24后细胞凋亡率为11.2%-46.2%,部分细胞呈现典型的凋亡形态学改变。结论：白花丹素能通过抑制细胞增殖,诱导细胞凋亡对膀胱癌T24的生长发挥明显的抑制的作用。本研究为进一步研究白花丹素抗癌机制奠定了基础。
目的：研究白花丹素对膀胱癌T24细胞侵袭和迁移能力的影响及其与Twist和MMP-9表达之间的关系。方法：通过划痕试验和Transwell小室实验检测白花丹素对T24细胞迁移和侵袭能力的影响。通过RT-PCR方法检测白花丹素对T24细胞NF-κB, Twsit和MMP-9 mRNA表达水平的影响,Western blot方法检测白花丹素对T24细胞NF-κB, Twsit和MMP-9蛋白表达水平的影响。用NF-κB激活-核转运检测试剂盒检测白花丹素干预后T24细胞NF-κB核转位的影响。结果：1-5uM白花丹素明显的抑制了T24细胞的迁移和侵袭能力(P<0.05)。1-10uM白花丹素抑制NF-κB, Twsit和MMP-9 mRNA和蛋白的表达水平。20uM白花丹素明显的降低了T24细胞核内NF-κB的蛋白水平。结论：白花丹素明显的抑制了T24细胞迁移和侵袭能力,同时抑制了NF-κB, Twsit和MMP-9 mRNA和蛋白的表达水平。
目的：研究异甘草酸镁(MgIG)对酒精所致小鼠睾丸氧化损伤的预防保护作用。方法：64只成年雄性昆明小鼠随机分成正常对照组、模型对照组、MgIG小剂量治疗组、MgIG大剂量治疗组。正常对照组每天予以0.4ml生理盐水灌胃；其余三组予以56%白酒连续灌胃18d(2个生精周期),剂量为16ml/kg。正常对照组和模型对照组在灌胃前45min予以0.75ml生理盐水腹腔注射；MgIG小剂量治疗组和MgIG大剂量治疗组灌胃前预防性给与异甘草酸镁腹腔注射(剂量分别为15mg/kg.d,45mg/kg.d)。干预9天和18天后分别处死小鼠,并作睾丸组织病理切片,HE染色及TUNEL染色,观察睾丸组织变化及睾丸细胞凋亡情况；检查各组小鼠精子数目和活动率改变；检测各组小鼠睾丸组织SOD、MDA、GSH-PX的含量。结果：异甘草酸镁有效的保护了酒精诱导的生精上皮的紊乱,支持细胞和精子细胞的退化和凋亡。异甘草酸镁干预组小鼠的精子计数及精子活动率明显的比模型对照组要高,但是比正常对照组要低。异甘草酸镁能够降低睾丸组织MDA,增加SOD和GSH-PX的含量,说明异甘草酸镁有抗酒精诱导的氧化损伤的作用。结论：大量饮酒即可引起小鼠睾丸氧化损伤,异甘草酸镁可以作为一种预防性的抗氧化剂减轻这种氧化损伤。
目的：研究体外补充异甘草酸镁对过氧化氢(H2O2)诱导的正常男性精子氧化损伤的干预作用。方法：收集正常生育男性的精液标本,精子PBS洗涤离心后用RPMI-1640培养基制作精子悬液,用加入不同浓度的异甘草酸镁或者600uM维生素C 37℃孵育30min后,再用200uM H2O2处理各组精子悬液,37℃孵育90min后分析各组精子悬液的精子活率、精子凋亡率和精子DNA完整性。结果：20ug/ml-0.5mg/ml的异甘草酸镁和600uM维生素C能明显的减轻200uM H2O2诱导的精子活率下降、凋亡率增加和DNA完整性的破坏(P<0.05),而2.5mg/ml的异甘草酸镁对此没有明显的保护作用(P>0.05)。各组药物的保护效果为0.1mg/ml异甘草酸镁>0.5mg/ml异甘草酸镁>600uM维生素C>20ug/ml异甘草酸镁。结论：体外补充0.1mg/ml异甘草酸镁能明显的保护H2O2诱导的精子氧化损伤。
Objective:To explore the growth inhibition and apoptosis inducing effects of Plumbagin on human bladder cancer T-24 cell line. Methods:After administration of 1-20 umol/L Plumbagin for 24-72 h, cell proliferation of T-24 cells were studied by MTT colorimetry. Cell proliferation ability also was detected by colony formation assay. Cellular apoptosis was inspected by acridine orange-ethidium bromide fluorescent staining, Hoechst 33258 fluorescent staining, and Annexin V-FITC and propidium iodide staining flow cytometry(FCM). Results:Plumbagin could inhibit the growth of T-24 in a dose-and time-dependent manner. After administration of 1 to 20 umol/L of Plumbagin for 24 h, the cell proliferation rates of cells decreased 1.7% to 88.1%. After being treated by 1-3 umol/L of Plumbagin, cell clone formation rates were dramatic decline. Partial cells presented the characteristic morphological changes of apoptosis. The cellular apoptotic rates induced by 2.5 umol/L to 10 umol/L Plumbagin for 24 h were 11.2% to 46.2%. Conclusion: Plumbagin could significantly inhibit the growth of T-24 cells by suppressing proliferation and inducing cell apoptosis, which lays the groundwork for further investigation into the mechanisms of anti-tumor effects of Plumbagin.
Objective To investigate the inhibitory effects of plumbagin on the invasion and migration and its correlation with Twist and matrix metalloproteinase-9 (MMP-9) in bladder cancer T24 cells. Methods:The cell migration and invasion were measured by Wound healing assay and Transwell chamber assay. The mRNA and protein levels of nuclear factorκB (NF-κB), Twsit and MMP-9 were evaluated by semiquantitative reverse transcription polymerase chain reaction and western blotting. Also, NF-κB nuclear translocation were analyzed by NF-κB Activation, Nuclear Translocation Assay Kit. Results:In this study, 1-5uM plumbagin had exhibited an inhibitory effect on the abilities of migration and invasion (P< 0.05). The mRNA and protein levels of NF-κB, Twsit and MMP-9 were significantly reduced by 1-10uM plumbagin treatment. Next, lOuM plumbagin significantly decreased the nuclear levels of NF-κB. Conclusion:We demonstrated the inhibitory effects of plumbagin on the invasion, migration and of T24 cells, while plumbagin treatment may decrease the expressions NF-κB, Twsit and MMP-9.
Objective:Ethanol treatment induces an increase in oxidative stress. As licorice compounds are potent antioxidants, our aim was to examine whether magnesium isoglycyrrhizinate attenuated lipid peroxidation, the major end-point of oxidative damage resulting from ethanol administration. Methods:Four groups(18 animals in each group) of male Kunming mice were used. The first group served as control and received 0.4ml normal saline daily for 18 days orally. The second group of mice was given 56% ethanol at 16ml/kg body weight per day for 18 days orally. The third group was given the same dose of ethanol and administrated magnesium isoglycyrrhizinate (15mg/kg.d, i.p.) for 18 days. The fourth group was given the same dose of ethanol and administrated with magnesium isoglycyrrhizinate (45m g/kg.d, i.p.) for 18 days. Twenty four hours after 9 days or 18 days of treatment the mice were sacrificed using 10% chloral hydrate. Sperm counts and motility in the epididymis were assessed. The lipid peroxidation and antioxidants of testicular mitochondria were also determined. The pathological changes of testicle tissue of the mice were observed by light microscopy. Results:Magnesium isoglycyrrhizinate effectively prevented the ethanol-induced seminiferous epithelium disorganization and degeneration of Sertoli cells and germ cells. Sperm counts and motility of the magnesium isoglycyrrhizinate treated groups were higher than those of the alcohol treated group, but were lower than those of the control group. The drug exhibited an ability to counteract ethanol induced oxidative challenge as it effectively reduced testicular malondialdehyde (MDA) and increased the activities of superoxide dismutase and glutathione peroxidase Conclusion: Magnesium isoglycyrrhizinate is able to inhibit the ethanol-induced lipid peroxidation and has a protective effect against testicular oxidative injury.
Objective:To study the antioxidant effects of the Magnesium isoglycyrrhizinate on hydrogen peroxide-mediated sperm oxidative damage in vitro. Methods:Pre-treatment fertile male semen suspensions 30min with Magnesium isoglycyrrhizinate at doses of 20ug/ml-2.5mg/ml and 600 um ascorbic acid,200uM hydrogen peroxide induced oxidative damage, then assessed sperm viability, apoptosis rate and sperm DNA integrity after 90min by eosin-Y, Wright-Giemsa staining and acridine orange fluorescence staining. Results: 20ug/ml-0.5mg/ml significantly protected sperm DNA against oxidative damage,600 um ascorbic acid also protected(P<0.05).2.5 mg/ml Magnesium isoglycyrrhizinate had no obvious protective effect(P>0.05). Compared with ascorbic acid added at physiological concentrations(600uM),0.1mg/ml Magnesium isoglycyrrhizinate was the most potent antioxidant, followed by 0.5 mg/ml Magnesium isoglycyrrhizinate, ascorbic acid,20ug/ml Magnesium isoglycyrrhizinate. Conclusion:Magnesium isoglycyrrhizinate reduces hydrogen peroxide-mediated sperm oxidative damage in vitro. Magnesium isoglycyrrhizinate may have a role to play in antioxidant protection against male infertility.
目的：研究白花丹素对膀胱癌T24细胞侵袭和迁移能力的影响及其与Twist和MMP-9表达之间的关系。方法：通过划痕试验和Transwell小室实验检测白花丹素对T24细胞迁移和侵袭能力的影响。通过RT-PCR方法检测白花丹素对T24细胞NF-κB, Twsit和MMP-9 mRNA表达水平的影响,Western blot方法检测白花丹素对T24细胞NF-κB, Twsit和MMP-9蛋白表达水平的影响。用NF-κB激活-核转运检测试剂盒检测白花丹素干预后T24细胞NF-κB核转位的影响。结果：1-5uM白花丹素明显的抑制了T24细胞的迁移和侵袭能力(P<0.05)。1-10uM白花丹素抑制NF-κB, Twsit和MMP-9 mRNA和蛋白的表达水平。20uM白花丹素明显的降低了T24细胞核内NF-κB的蛋白水平。结论：白花丹素明显的抑制了T24细胞迁移和侵袭能力,同时抑制了NF-κB, Twsit和MMP-9 mRNA和蛋白的表达水平。
目的：研究异甘草酸镁(MgIG)对酒精所致小鼠睾丸氧化损伤的预防保护作用。方法：64只成年雄性昆明小鼠随机分成正常对照组、模型对照组、MgIG小剂量治疗组、MgIG大剂量治疗组。正常对照组每天予以0.4ml生理盐水灌胃；其余三组予以56%白酒连续灌胃18d(2个生精周期),剂量为16ml/kg。正常对照组和模型对照组在灌胃前45min予以0.75ml生理盐水腹腔注射；MgIG小剂量治疗组和MgIG大剂量治疗组灌胃前预防性给与异甘草酸镁腹腔注射(剂量分别为15mg/kg.d,45mg/kg.d)。干预9天和18天后分别处死小鼠,并作睾丸组织病理切片,HE染色及TUNEL染色,观察睾丸组织变化及睾丸细胞凋亡情况；检查各组小鼠精子数目和活动率改变；检测各组小鼠睾丸组织SOD、MDA、GSH-PX的含量。结果：异甘草酸镁有效的保护了酒精诱导的生精上皮的紊乱,支持细胞和精子细胞的退化和凋亡。异甘草酸镁干预组小鼠的精子计数及精子活动率明显的比模型对照组要高,但是比正常对照组要低。异甘草酸镁能够降低睾丸组织MDA,增加SOD和GSH-PX的含量,说明异甘草酸镁有抗酒精诱导的氧化损伤的作用。结论：大量饮酒即可引起小鼠睾丸氧化损伤,异甘草酸镁可以作为一种预防性的抗氧化剂减轻这种氧化损伤。
目的：研究体外补充异甘草酸镁对过氧化氢(H2O2)诱导的正常男性精子氧化损伤的干预作用。方法：收集正常生育男性的精液标本,精子PBS洗涤离心后用RPMI-1640培养基制作精子悬液,用加入不同浓度的异甘草酸镁或者600uM维生素C 37℃孵育30min后,再用200uM H2O2处理各组精子悬液,37℃孵育90min后分析各组精子悬液的精子活率、精子凋亡率和精子DNA完整性。结果：20ug/ml-0.5mg/ml的异甘草酸镁和600uM维生素C能明显的减轻200uM H2O2诱导的精子活率下降、凋亡率增加和DNA完整性的破坏(P<0.05),而2.5mg/ml的异甘草酸镁对此没有明显的保护作用(P>0.05)。各组药物的保护效果为0.1mg/ml异甘草酸镁>0.5mg/ml异甘草酸镁>600uM维生素C>20ug/ml异甘草酸镁。结论：体外补充0.1mg/ml异甘草酸镁能明显的保护H2O2诱导的精子氧化损伤。
Objective:To explore the growth inhibition and apoptosis inducing effects of Plumbagin on human bladder cancer T-24 cell line. Methods:After administration of 1-20 umol/L Plumbagin for 24-72 h, cell proliferation of T-24 cells were studied by MTT colorimetry. Cell proliferation ability also was detected by colony formation assay. Cellular apoptosis was inspected by acridine orange-ethidium bromide fluorescent staining, Hoechst 33258 fluorescent staining, and Annexin V-FITC and propidium iodide staining flow cytometry(FCM). Results:Plumbagin could inhibit the growth of T-24 in a dose-and time-dependent manner. After administration of 1 to 20 umol/L of Plumbagin for 24 h, the cell proliferation rates of cells decreased 1.7% to 88.1%. After being treated by 1-3 umol/L of Plumbagin, cell clone formation rates were dramatic decline. Partial cells presented the characteristic morphological changes of apoptosis. The cellular apoptotic rates induced by 2.5 umol/L to 10 umol/L Plumbagin for 24 h were 11.2% to 46.2%. Conclusion: Plumbagin could significantly inhibit the growth of T-24 cells by suppressing proliferation and inducing cell apoptosis, which lays the groundwork for further investigation into the mechanisms of anti-tumor effects of Plumbagin.
Objective To investigate the inhibitory effects of plumbagin on the invasion and migration and its correlation with Twist and matrix metalloproteinase-9 (MMP-9) in bladder cancer T24 cells. Methods:The cell migration and invasion were measured by Wound healing assay and Transwell chamber assay. The mRNA and protein levels of nuclear factorκB (NF-κB), Twsit and MMP-9 were evaluated by semiquantitative reverse transcription polymerase chain reaction and western blotting. Also, NF-κB nuclear translocation were analyzed by NF-κB Activation, Nuclear Translocation Assay Kit. Results:In this study, 1-5uM plumbagin had exhibited an inhibitory effect on the abilities of migration and invasion (P< 0.05). The mRNA and protein levels of NF-κB, Twsit and MMP-9 were significantly reduced by 1-10uM plumbagin treatment. Next, lOuM plumbagin significantly decreased the nuclear levels of NF-κB. Conclusion:We demonstrated the inhibitory effects of plumbagin on the invasion, migration and of T24 cells, while plumbagin treatment may decrease the expressions NF-κB, Twsit and MMP-9.
Objective:Ethanol treatment induces an increase in oxidative stress. As licorice compounds are potent antioxidants, our aim was to examine whether magnesium isoglycyrrhizinate attenuated lipid peroxidation, the major end-point of oxidative damage resulting from ethanol administration. Methods:Four groups(18 animals in each group) of male Kunming mice were used. The first group served as control and received 0.4ml normal saline daily for 18 days orally. The second group of mice was given 56% ethanol at 16ml/kg body weight per day for 18 days orally. The third group was given the same dose of ethanol and administrated magnesium isoglycyrrhizinate (15mg/kg.d, i.p.) for 18 days. The fourth group was given the same dose of ethanol and administrated with magnesium isoglycyrrhizinate (45m g/kg.d, i.p.) for 18 days. Twenty four hours after 9 days or 18 days of treatment the mice were sacrificed using 10% chloral hydrate. Sperm counts and motility in the epididymis were assessed. The lipid peroxidation and antioxidants of testicular mitochondria were also determined. The pathological changes of testicle tissue of the mice were observed by light microscopy. Results:Magnesium isoglycyrrhizinate effectively prevented the ethanol-induced seminiferous epithelium disorganization and degeneration of Sertoli cells and germ cells. Sperm counts and motility of the magnesium isoglycyrrhizinate treated groups were higher than those of the alcohol treated group, but were lower than those of the control group. The drug exhibited an ability to counteract ethanol induced oxidative challenge as it effectively reduced testicular malondialdehyde (MDA) and increased the activities of superoxide dismutase and glutathione peroxidase Conclusion: Magnesium isoglycyrrhizinate is able to inhibit the ethanol-induced lipid peroxidation and has a protective effect against testicular oxidative injury.
Objective:To study the antioxidant effects of the Magnesium isoglycyrrhizinate on hydrogen peroxide-mediated sperm oxidative damage in vitro. Methods:Pre-treatment fertile male semen suspensions 30min with Magnesium isoglycyrrhizinate at doses of 20ug/ml-2.5mg/ml and 600 um ascorbic acid,200uM hydrogen peroxide induced oxidative damage, then assessed sperm viability, apoptosis rate and sperm DNA integrity after 90min by eosin-Y, Wright-Giemsa staining and acridine orange fluorescence staining. Results: 20ug/ml-0.5mg/ml significantly protected sperm DNA against oxidative damage,600 um ascorbic acid also protected(P<0.05).2.5 mg/ml Magnesium isoglycyrrhizinate had no obvious protective effect(P>0.05). Compared with ascorbic acid added at physiological concentrations(600uM),0.1mg/ml Magnesium isoglycyrrhizinate was the most potent antioxidant, followed by 0.5 mg/ml Magnesium isoglycyrrhizinate, ascorbic acid,20ug/ml Magnesium isoglycyrrhizinate. Conclusion:Magnesium isoglycyrrhizinate reduces hydrogen peroxide-mediated sperm oxidative damage in vitro. Magnesium isoglycyrrhizinate may have a role to play in antioxidant protection against male infertility.
引文
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14. Schiavi RC, Stimmel BB, Mandeli J, White D. Chronic alcoholism and male sexual function. Am J Psychiatry 1995; 152:1045-51.
15. Rosenblum ER, Gavaler JS, Van Thiel DH. Lipid peroxidation:a mechanism for ethanol-associated testicular injury in rats. Endocrinol 1985; 116:311-8.
16. Emanuele MA, Emanuele N. Alcohol and the male reproductive system. Alcohol Res Health 2001; 25:282-7.
17. Richier S, Furla P, Plantivaux A, Merle P, Allemand D. Symbiosis-induced adaptation to oxidative stress. J. Exp. Biol.2005; 208:277-85.
18. Maneesh M, Dutta S, Chakrabarti A, Vasudevan DM. Experimental therapeutic intervention with alpha tocopherol in ethanol induced testicular injuries in rats. IJCB 2007; 22:138-42.
19. Ambrosini, A., et al., Oleoylethanolamide protects human sperm cells from oxidation stress:studies on cases of idiopathic infertility. Biol Reprod,2006.74(4):p.659-65.
20. Aitken, R.J. and J.S. Clarkson, Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil,1987.81(2):p.459-69.
21. Sierens, J., et al., In vitro isoflavone supplementation reduces hydrogen peroxide-induced DNA damage in sperm. Teratog Carcinog Mutagen,2002.22(3):p. 227-34.
22. Lissak, A., et al., Oxidative stress indices in seminal plasma, as measured by the thermochemiluminescence assay, correlate with sperm parameters. Fertil Steril,2004. 81 Suppl1:p.792-7.
23. Rivlin, J., et al., Role of hydrogen peroxide in sperm capacitation and acrosome reaction. Biol Reprod,2004.70(2):p.518-22.
24. Kemal Duru, N., M. Morshedi,and S. Oehninger, Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Fertil Steril,2000. 74(6):p.1200-7.
25. Pasqualotto, F.F., et al., Relationship between oxidative stress, semen characteristics, and clinical diagnosis in men undergoing infertility investigation. Fertil Steril,2000. 73(3):p.459-64.
26. Sikka, S.C., Relative impact of oxidative stress on male reproductive function. Curr Med Chem,2001.8(7):p.851-62.
27. Dobrzynska, M.M., A. Baumgartner, and D. Anderson, Antioxidants modulate thyroid hormone-and noradrenaline-induced DNA damage in human sperm. Mutagenesis, 2004.19(4):p.325-30.
28. Aziz, N., et al., Novel association between sperm reactive oxygen species production, sperm morphological defects, and the sperm deformity index. Fertil Steril,2004. 81(2):p.349-54.
29. Fraczek, M. and M. Kurpisz, The redox system in human semen and peroxidative damage of spermatozoa. Postepy Hig Med Dosw (Online),2005.59:p.523-34.
30. Lemkecher, T., et al., Leucocytospermia, oxidative stress and male fertility:facts and hypotheses. Gynecol Obstet Fertil,2005.33(1-2):p.2-10.
31. Aitken, R.J. and M.A. Baker, Oxidative stress, sperm survival and fertility control. Mol Cell Endocrinol,2006.250(1-2):p.66-9.
32. Zorn, B., G. Vidmar, and H. Meden-Vrtovec, Seminal reactive oxygen species as predictors of fertilization, embryo quality and pregnancy rates after conventional in vitro fertilization and intracytoplasmic sperm injection. Int J Androl,2003.26(5):p. 279-85.
33. Hammadeh, M.E., et al., Comparison of reactive oxygen species concentration in seminal plasma and semen parameters in partners of pregnant and non-pregnant patients after IVF/ICSI. Reprod Biomed Online,2006.13(5):p.696-706.
34. Chi, H.J., et al., Protective effect of antioxidant supplementation in sperm-preparation medium against oxidative stress in human spermatozoa. Hum Reprod,2008.23(5):p. 1023-8.
35. Sun L, Shen JF, Pang XY, Lu LG, Mao YM, Zeng MD. Phase Ⅰ safety and pharmacokinetic study of magnesium isoglycyrrhizinate after single and multiple intravenous doses in Chinese healthy volunteers. J Clin Pharmacol 2007; 47:767-73.
36. Bao QD, Yang LL, Wang L, Cui DL. Protective effects of magnesium isoglycyrrhizinate against carbon tetrachloride-induced acute liver injury in mice. World Chinese J Digestology 2008; 16:1004-7.
37. Dong LP, Yu F, Liu J, Mu XM. Protective efect of magnesium isoglycyrrhizinate on acute hepatic inury in mice. China Pharmacy 2006; 17:902-4.
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10. Srinivas, P., et al., Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells. Mol Carcinog,2004.40(4):p.201-11.
11. Xu, K.H. and D.P. Lu, Plumbagin induces ROS-mediated apoptosis in human promyelocytic leukemia cells in vivo. Leuk Res,2009.
12. Shih, Y.W., et al., Plumbagin inhibits invasion and migration of liver cancer HepG2 cells by decreasing productions of matrix metalloproteinase-2 and urokinase-plasminogen activator. Hepatol Res,2009.39(10):p.998-1009.
13. Chen, C.A., et al., Plumbagin, Isolated from Plumbago zeylanica, Induces Cell Death through Apoptosis in Human Pancreatic Cancer Cells. Pancreatology.9(6):p. 797-809.
14. Zhao, Y.L. and D.P. Lu, Effects of plumbagin on the human acute promyelocytic leukemia cells in vitro. Zhongguo Shi Yan Xue Ye Xue Za Zhi,2006.14(2):p. 208-11.
15. Thasni, K.A., et al., Estrogen-dependent cell signaling and apoptosis in BRCA1-blocked BG1 ovarian cancer cells in response to plumbagin and other chemotherapeutic agents. Ann Oncol,2008.19(4):p.696-705.
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18. Ahmad, A., et al., Plumbagin-induced apoptosis of human breast cancer cells is mediated by inactivation of NF-kappaB and Bcl-2. J Cell Biochem,2008.105(6):p. 1461-71.
19. Kuo, P.L., Y.L. Hsu, and C.Y. Cho, Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells. Mol Cancer Ther,2006.5(12):p.3209-21.
1. Cookson. M.S., et al., The treated natural history of high risk superficial bladder cancer:15-year outcome. J Urol,1997.158(1):p.62-7.
2. Shahin,O., et al., A retrospective analysis of 153 patients treated with or without intravesical bacillus Calmette-Guerin for primary stage T1 grade 3 bladder cancer: recurrence, progression and survival. J Urol,2003.169(1):p.96-100; discussion 100.
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5. Hadaschik, B.A., et al., Intravesical chemotherapy of high-grade bladder cancer with HTI-286, a synthetic analogue of the marine sponge product hemiasterlin. Clin Cancer Res,2008.14(5):p.1510-8.
6. Nazeem, S., et al., Plumbagin induces cell death through a copper-redox cycle mechanism in human cancer cells. Mutagenesis,2009.24(5):p.413-8.
7. Srinivas, P., et al., Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells. Mol Carcinog,2004.40(4):p.201-11.
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1. Ambrosini, A., et al., Oleoylethanolamide protects human sperm cells from oxidation stress:studies on cases of idiopathic infertility. Biol Reprod,2006.74(4):p.659-65.
2. Aitken, R.J. and J.S. Clarkson, Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil,1987.81(2):p.459-69.
3. Sierens, J., et al., In vitro isoflavone supplementation reduces hydrogen peroxide-induced DNA damage in sperm. Teratog Carcinog Mutagen,2002.22(3):p. 227-34.
4. Lissak, A., et al., Oxidative stress indices in seminal plasma, as measured by the thermochemiluminescence assay, correlate with sperm parameters. Fertil Steril,2004. 81Suppl1:p.792-7.
5. Rivlin, J., et al., Role of hydrogen peroxide in sperm capacitation and acrosome reaction. Biol Reprod,2004.70(2):p.518-22.
6. Kemal Duru, N., M. Morshedi, and S. Oehninger, Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Fertil Steril,2000. 74(6):p.1200-7.
7. Pasqualotto, F.F., et al., Relationship between oxidative stress, semen characteristics, and clinical diagnosis in men undergoing infertility investigation. Fertil Steril,2000. 73(3):p.459-64.
8. Sikka, S.C., Relative impact of oxidative stress on male reproductive function. Curr Med Chem,2001.8(7):p.851-62.
9. Dobrzynska, M.M., A. Baumgartner. and D. Anderson, Antioxidants modulate thyroid hormone-and noradrenaline-induced DNA damage in human sperm. Mutagenesis, 2004.19(4):p.325-30.
10. Aziz, N., et al., Novel association between sperm reactive oxygen species production, sperm morphological defects, and the sperm deformity index. Fertil Steril,2004. 81(2):p.349-54.
11. Fraczek, M. and M. Kurpisz, The redox system in human semen and peroxidative damage of spermatozoa. Postepy Hig Med Dosw (Online),2005.59:p.523-34.
12. Lemkecher, T., et al., Leucocytospermia, oxidative stress and male fertility:facts and hypotheses. Gynecol Obstet Fertil,2005.33(1-2):p.2-10.
13. Aitken, R.J. and M.A. Baker, Oxidative stress, sperm survival and fertility control. Mol Cell Endocrinol,2006.250(1-2):p.66-9.
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17. Sun L, Shen JF, Pang XY, Lu LG, Mao YM, Zeng MD. Phase I safety and pharmacokinetic study of magnesium isoglycyrrhizinate after single and multiple intravenous doses in Chinese healthy volunteers. J Clin Pharmacol 2007; 47:767-73.
18. Bao QD, Yang LL, Wang L, Cui DL. Protective effects of magnesium isoglycyrrhizinate against carbon tetrachloride-induced acute liver injury in mice. World Chinese J Digestology 2008; 16:1004-7.
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1. Zhao, Y.L. and D.P. Lu, [Effects of plumbagin on the human acute promyelocytic leukemia cells in vitro]. Zhongguo Shi Yan Xue Ye Xue Za Zhi,2006.14(2):p. 208-11.
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3. Nazeem, S., et al., Plumbagin induces cell death through a copper-redox cycle mechanism in human cancer cells. Mutagenesis,2009.24(5):p.413-8.
4. Wang, C.C., et al., Plumbagin induces cell cycle arrest and apoptosis through reactive oxygen species/c-Jun N-terminal kinase pathways in human melanoma A375.S2 cells. Cancer Lett,2008.259(1):p.82-98.
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15. Srinivas, G, et al., Antisense blocking of BRCA1 enhances sensitivity to plumbagin but not tamoxifen in BG-1 ovarian cancer cells. Mol Carcinog,2004.39(1):p.15-25.
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17. Srinivas. P., et al., Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells. Mol Carcinog,2004.40(4):p.201-11.
18. Hsu, Y.L., et al., Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) induces apoptosis and cell cycle arrest in A549 cells through p53 accumulation via c-Jun NH2-terminal kinase-mediated phosphorylation at serine 15 in vitro and in vivo. J Pharmacol Exp Ther,2006.318(2):p.484-94.
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22. Ahmad, A., et al., Plumbagin-induced apoptosis of human breast cancer cells is mediated by inactivation of NF-kappaB and Bcl-2. J Cell Biochem,2008.105(6):p. 1461-71.
23. Aziz, M.H., N.E. Dreckschmidt,and A.K. Verma, Plumbagin, a Medicinal Plant-Derived Naphthoquinone, Is a Novel Inhibitor of the Growth and Invasion of Hormone-Refractory Prostate Cancer. Cancer Res,2008.68(21):p.9024-9032.
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8. Nazeem, S., et al., Plumbagin induces cell death through a copper-redox cycle mechanism in human cancer cells. Mutagenesis,2009.24(5):p.413-8.
9. Srinivas, P., et al., Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells. Mol Carcinog,2004.40(4):p.201-11.
10. Xu, K.H. and D.P. Lu, Plumbagin induces ROS-mediated apoptosis in human promyelocytic leukemia cells in vivo. Leuk Res,2009.
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13. Wang, X., et al., Identification of a novel function of TWIST, a bHLH protein, in the development of acquired taxol resistance in human cancer cells. Oncogene, 2004.23(2):p.474-82.
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10. Villalta J, Ballesca JL, Nicolas JM, Martinez de Osaba MJ, Antunez E, Pimentel C. Testicular function in asymptomatic chronic alcoholics:Relation to ethanol intake. Alcoholism Clin Exp Res 1997; 21:128-33.
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16. Emanuele MA, Emanuele N. Alcohol and the male reproductive system. Alcohol Res Health 2001; 25:282-7.
17. Richier S, Furla P, Plantivaux A, Merle P, Allemand D. Symbiosis-induced adaptation to oxidative stress. J. Exp. Biol.2005; 208:277-85.
18. Maneesh M, Dutta S, Chakrabarti A, Vasudevan DM. Experimental therapeutic intervention with alpha tocopherol in ethanol induced testicular injuries in rats. IJCB 2007; 22:138-42.
19. Ambrosini, A., et al., Oleoylethanolamide protects human sperm cells from oxidation stress:studies on cases of idiopathic infertility. Biol Reprod,2006.74(4):p.659-65.
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3. Dalbagni, G, The management of superficial bladder cancer. Nat Clin Pract Urol, 2007.4(5):p.254-60.
4. Amiel, GE. and S.P. Lerner, Combining surgery and chemotherapy for invasive bladder cancer:current and future directions. Expert Rev Anticancer Ther,2006.6(2): p.281-91.
5. Cookson, M.S., et al., The treated natural history of high risk superficial bladder cancer:15-year outcome. J Urol,1997.158(1):p.62-7.
6. Shahin, O., et al., A retrospective analysis of 153 patients treated with or without intravesical bacillus Calmette-Guerin for primary stage T1 grade 3 bladder cancer: recurrence, progression and survival. J Urol,2003.169(1):p.96-100; discussion 100.
7. Kanehira, M., et al., Oncogenic role of MPHOSPH1, a cancer-testis antigen specific to human bladder cancer. Cancer Res,2007.67(7):p.3276-85.
8. Hadaschik, B.A., et al., Intravesical chemotherapy of high-grade bladder cancer with HTI-286, a synthetic analogue of the marine sponge product hemiasterlin. Clin Cancer Res,2008.14(5):p.1510-8.
9. Nazeem, S., et al., Plumbagin induces cell death through a copper-redox cycle mechanism in human cancer cells. Mutagenesis,2009.24(5):p.413-8.
10. Srinivas, P., et al., Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells. Mol Carcinog,2004.40(4):p.201-11.
11. Xu, K.H. and D.P. Lu, Plumbagin induces ROS-mediated apoptosis in human promyelocytic leukemia cells in vivo. Leuk Res,2009.
12. Shih, Y.W., et al., Plumbagin inhibits invasion and migration of liver cancer HepG2 cells by decreasing productions of matrix metalloproteinase-2 and urokinase-plasminogen activator. Hepatol Res,2009.39(10):p.998-1009.
13. Chen, C.A., et al., Plumbagin, Isolated from Plumbago zeylanica, Induces Cell Death through Apoptosis in Human Pancreatic Cancer Cells. Pancreatology.9(6):p. 797-809.
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1. Cookson. M.S., et al., The treated natural history of high risk superficial bladder cancer:15-year outcome. J Urol,1997.158(1):p.62-7.
2. Shahin,O., et al., A retrospective analysis of 153 patients treated with or without intravesical bacillus Calmette-Guerin for primary stage T1 grade 3 bladder cancer: recurrence, progression and survival. J Urol,2003.169(1):p.96-100; discussion 100.
3. Rosenberg, J.E. and W.C. Hahn, Bladder cancer:modeling and translation. Genes Dev, 2009.23(6):p.655-9.
4. Kanehira, M., et al., Oncogenic role of MPHOSPH1, a cancer-testis antigen specific to human bladder cancer. Cancer Res,2007.67(7):p.3276-85.
5. Hadaschik, B.A., et al., Intravesical chemotherapy of high-grade bladder cancer with HTI-286, a synthetic analogue of the marine sponge product hemiasterlin. Clin Cancer Res,2008.14(5):p.1510-8.
6. Nazeem, S., et al., Plumbagin induces cell death through a copper-redox cycle mechanism in human cancer cells. Mutagenesis,2009.24(5):p.413-8.
7. Srinivas, P., et al., Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells. Mol Carcinog,2004.40(4):p.201-11.
8. Xu, K.H. and D.P. Lu, Plumbagin induces ROS-mediated apoptosis in human promyelocytic leukemia cells in vivo. Leuk Res,2009.
9. Shih, Y.W., et al., Plumbagin inhibits invasion and migration of liver cancer HepG2 cells by decreasing productions of matrix metalloproteinase-2 and urokinase-plasminogen activator. Hepatol Res,2009.39(10):p.998-1009.
10. Chen, C.A., et al., Plumbagin, Isolated from Plumbago zeylanica, Induces Cell Death through Apoptosis in Human Pancreatic Cancer Cells. Pancreatology.9(6):p. 797-809.
11. Cheng, G.Z., et al., Twist Transcriptionally Up-regulates AKT2 in Breast Cancer Cells Leading to Increased Migration, Invasion, and Resistance to Paclitaxel. Cancer Res, 2007.67(5):p.1979-1987.
12. Figueira, R., et al., Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential. BMC Cancer,2009.9(1):p.20.
13. Momeny, M., et al., Silibinin inhibits invasive properties of human glioblastoma U87MG cells through suppression of cathepsin B and nuclear factor kappa B-mediated induction of matrix metalloproteinase 9. Anticancer Drugs.2010.21(3):p. 252-60.
14. Pham, C.G., et al., Upregulation of Twist-1 by NF-κB Blocks Cytotoxicity Induced by Chemotherapeutic Drugs. Mol. Cell. Biol.,2007.27(11):p.3920-3935.
15. Sethi, G., B. Sung, and B.B. Aggarwal, Nuclear factor-kappaB activation:from bench to bedside. Exp Biol Med (Maywood),2008.233(1):p.21-31.
16. 殷积彬,刘铁夫,孟祥宁,等.NS-398对HGF诱导的肝癌细胞株MMP-7, MMP-9, TIMP-1表达的影响.世界华人消化杂志.2006；14(23)：2301-2305.
17. 储著凌,谢敏,潘一明,朱海涛.NF-κB反义核酸对胰腺癌细胞ICAM-1表达及 侵袭转移能力的影响.肿瘤防治研究.2007,34(12)：908-911.
18. Wang, X., et al., Identification of a novel function of TWIST, a bHLH protein, in the development of acquired taxol resistance in human cancer cells. Oncogene,2004. 23(2):p.474-82.
19. Zhang, Z., et al., Significance of TWIST expression and its association with E-cadherin in bladder cancer. Hum Pathol,2007.38(4):p.598-606.
20. Kwok, W.K., et al., Up-Regulation of TWIST in Prostate Cancer and Its Implication as a Therapeutic Target. Cancer Res,2005.65(12):p.5153-5162.
21. 徐江锋,罗庚求,余丹.Twist基因对胃癌细胞中AP-1转录活性及MMP-9表达的影响.实用预防医学.2008,15(5)：1333-1335.
1. Eagon PK, Elm MS, Tadic SD, Nanji AA. Down regulation of nuclear sex steroid receptor activity correlates with severity of alcoholic liver injury. Am J Physiol Gastrointest Liver Physiol 2001; 281:342-9.
2. Villalta J, Ballesca JL, Nicolas JM, Martinez de Osaba MJ, Antunez E, Pimentel C. Testicular function in asymptomatic chronic alcoholics:Relation to ethanol intake. Alcoholism Clin Exp Res 1997; 21:128-33.
3. Wallock-Montelius LM, Villanueva JA, Chapin RE, Conley AJ, Nguyen HP, Ames BN, et al.Chronic ethanol perturbs testicular folate metabolism and dietary folate deficiency reduces sex hormone levels in the Yucatan micropig. Biol Reprod 2007; 76: 455-65.
4. Adler RA. Clinical review 33:Clinically important effects of alcohol on endocrine function. J Clin Endocrinol Metab 1992; 74:957-60.
5. Van Thiel DH, Lester R, Sherins RJ. Hypogonadism in alcoholic liver disease: Evidence for a double defect. Gastroenterol 1974; 67:1188-99.
6. Schiavi RC, Stimmel BB, Mandeli J, White D. Chronic alcoholism and male sexual function. Am J Psychiatry 1995; 152:1045-51.
7. Rosenblum ER, Gavaler JS, Van Thiel DH. Lipid peroxidation:a mechanism for ethanol-associated testicular injury in rats. Endocrinol 1985; 116:311-8.
8. Emanuele MA, Emanuele N. Alcohol and the male reproductive system. Alcohol Res Health 2001; 25:282-7.
9. Richier S, Furla P, Plantivaux A, Merle P, Allemand D. Symbiosis-induced adaptation to oxidative stress. J. Exp. Biol. 2005; 208:277-85.
10. Maneesh M, Dutta S, Chakrabarti A, Vasudevan DM. Experimental therapeutic intervention with alpha tocopherol in ethanol induced testicular injuries in rats. IJCB 2007; 22:138-42.
11. Sun L, Shen JF, Pang XY, Lu LG, Mao YM, Zeng MD. Phase I safety and pharmacokinetic study of magnesium isoglycyrrhizinate after single and multiple intravenous doses in Chinese healthy volunteers. J Clin Pharmacol 2007; 47:767-73.
12. Bao QD, Yang LL, Wang L, Cui DL. Protective effects of magnesium isoglycyrrhizinate against carbon tetrachloride-induced acute liver injury in mice. World Chinese JDigestology 2008; 16:1004-7.
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1. Ambrosini, A., et al., Oleoylethanolamide protects human sperm cells from oxidation stress:studies on cases of idiopathic infertility. Biol Reprod,2006.74(4):p.659-65.
2. Aitken, R.J. and J.S. Clarkson, Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil,1987.81(2):p.459-69.
3. Sierens, J., et al., In vitro isoflavone supplementation reduces hydrogen peroxide-induced DNA damage in sperm. Teratog Carcinog Mutagen,2002.22(3):p. 227-34.
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