蛇六谷提取物抑制K562细胞增殖并诱导分化的作用
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摘要
目的:探讨蛇六谷提取物(TuAKe)抑制人慢性髓系白血病K562细胞增殖和诱导分化的作用机制。方法:不同浓度的TuAKe处理K562细胞,MTT比色法和半固体集落形成实验检测K562细胞的增殖能力;瑞氏-姬姆萨染色观察细胞形态;流式细胞术检测分化相关抗原CD11b、CD14和CD42b的阳性表达率;Western blot法检测细胞周期蛋白依赖性激酶2(CDK2)、细胞周期蛋白E1(cyclin E1)和红系分化核转录因子GATA-1的蛋白表达水平。结果:TuAKe能够抑制K562细胞增殖,改变细胞形态,抑制K562细胞进入S期,并阻滞在G_2/M期,提高分化相关抗原CD11b、CD14和CD42b阳性表达率,上调GATA-1蛋白表达,同时下调CDK2和cyclin E1蛋白表达(P<0.05)。结论:TuAKe可能通过调控细胞周期抑制K562细胞增殖,同时诱导K562细胞多向分化。
AIM: To investigate the effects of Sheliugu extract(the extract from Amorphophallus konjac tuber, TuAKe) on the proliferation and differentiation of human chronic myeloid leukemia K562 cells. METHODS: TuAKe at different concentrations was used to treat with the K562 cells. The colony formation ability of the cells was detected by the colony formation assay with semi-solid culture. The viability of K562 cells was measured by MTT assay. The morphological changes of the cells were observed under microscope with Wright-Giemsa staining. The positive expression rates of differentiation-related antigens CD11 b, CD14 and CD42 b were analyzed by flow cytometry. The protein expression of cyclin-dependent kinase 2(CDK2), cyclin E1 and erythroid cell differentiation nuclear transcription factor GATA-1 was determined by Western blot. RESULTS: TuAKe reduced the proliferation of K562 cells, reduced nuclear mass ratio, inhibited K562 cells to enter S phase, and blocked the cells in G_2/M phase. TuAKe improved the positive expression rates of differentiation-related antigens CD11 b, CD14 and CD42 b, increased GATA-1 protein expression, and decreased the protein expression of CDK2 and cyclin E1(P<0.05). CONCLUSION: TuAKe may inhibit K562 cell proliferation by regulating cell cycle, and induce K562 cell multidirectional differentiation at the same time.
AIM: To investigate the effects of Sheliugu extract(the extract from Amorphophallus konjac tuber, TuAKe) on the proliferation and differentiation of human chronic myeloid leukemia K562 cells. METHODS: TuAKe at different concentrations was used to treat with the K562 cells. The colony formation ability of the cells was detected by the colony formation assay with semi-solid culture. The viability of K562 cells was measured by MTT assay. The morphological changes of the cells were observed under microscope with Wright-Giemsa staining. The positive expression rates of differentiation-related antigens CD11 b, CD14 and CD42 b were analyzed by flow cytometry. The protein expression of cyclin-dependent kinase 2(CDK2), cyclin E1 and erythroid cell differentiation nuclear transcription factor GATA-1 was determined by Western blot. RESULTS: TuAKe reduced the proliferation of K562 cells, reduced nuclear mass ratio, inhibited K562 cells to enter S phase, and blocked the cells in G_2/M phase. TuAKe improved the positive expression rates of differentiation-related antigens CD11 b, CD14 and CD42 b, increased GATA-1 protein expression, and decreased the protein expression of CDK2 and cyclin E1(P<0.05). CONCLUSION: TuAKe may inhibit K562 cell proliferation by regulating cell cycle, and induce K562 cell multidirectional differentiation at the same time.
引文
[1] 浙江省农业厅. 浙江农药志[M]. 杭州: 浙江人民出版社, 1959:53.
[2] 浙江省食品药品监督管理局. 浙江省中药炮制规范[M]. 杭州: 浙江科学技术出版社, 2005:98.
[3] 潘磊, 方美灵, 陈培丰. 中药蛇六谷石油醚萃取物诱导人胃癌细胞-凋亡的实验研究[J]. 中华中医药学刊, 2012, 30(6):1259-1261.
[4] Chen X, Yuan LQ, Li LJ, et al. Suppression of gastric cancer by extract from the tuber of Amorphophallus konjac via induction of apoptosis and autophagy[J]. Oncol Rep, 2017, 38(2):1051-1058.
[5] Siu KT, Rosner MR, MinellaAC. An integrated view of cyclin E function and regulation[J]. Cell Cycle, 2012, 11(1):57-64.
[6] Dulic V, Lees E, Reed SI. Association of human cyclin E with aperiodic G1-S phase protein kinase[J]. Science, 1992, 257(5078):1958-1961.
[7] Zschemisch NH, Liedtke C, Dierssen U, et al. Expression of a cyclinE1 isoform in mice is correlated with the quiescent cell cycle status of hepatocytes in vivo[J]. He-patology, 2006, 44(1):164-173.
[8] Leung SY, Ho C, Tu IP, et al. Comprehensive analysis of 19q12 amplicon in human[J]. Mod Pathol, 2006, 19(6):854-863.
[9] MtEumder S, DuPree EL, Almasan A. A dual role of cyclin E in cell proliferation and apoptosis may provide a target for cancer thempy[J]. Curt Cancer Drug Targets, 2004, 4(1):65-75.
[10] 余潇苓, 赵燕娜, 郑智茵, 等. 地西他滨抑制K562白血病细胞增殖和诱导分化的作用[J]. 中国病理生理杂志, 2017, 33(1):13-17.
[11] 王玉茹, 尹利明, 魏克民, 等. 黄芪注射液对白血病K562细胞诱导分化作用的研究[J]. 中国中医药科技, 2013, 20(2):146-148.
[12] 柯大智, 王红宁, 陈地龙, 等. 人参皂苷Rg1抑制白血病细胞K562增殖并诱导分化的分子机制[J]. 第三军医大学学报, 2014, 36(2):125-129.
[13] Squires MS, Feltell RE, Wallis NG, et al. Biological characterization of AT7519 a small-molecule inhibitor of cyclin-dependent kinases in human tumor celllines[J]. Mol Cancer Ther, 2009, 8(12):324-332.
[14] van Riggelen J, Felsher DW. Myc and a Cdk2 senescence switch[J]. Nat Cell Biol, 2010, 12(1):7-9.
[15] Xu L, Wang C, Wen Z, et al. Selective up-regulation of CDK2 is critical for TLR9 signaling stimulated proliferation of human lung cancer cell[J]. Immunol Lett, 2010, 127(2):93-99.
[2] 浙江省食品药品监督管理局. 浙江省中药炮制规范[M]. 杭州: 浙江科学技术出版社, 2005:98.
[3] 潘磊, 方美灵, 陈培丰. 中药蛇六谷石油醚萃取物诱导人胃癌细胞-凋亡的实验研究[J]. 中华中医药学刊, 2012, 30(6):1259-1261.
[4] Chen X, Yuan LQ, Li LJ, et al. Suppression of gastric cancer by extract from the tuber of Amorphophallus konjac via induction of apoptosis and autophagy[J]. Oncol Rep, 2017, 38(2):1051-1058.
[5] Siu KT, Rosner MR, MinellaAC. An integrated view of cyclin E function and regulation[J]. Cell Cycle, 2012, 11(1):57-64.
[6] Dulic V, Lees E, Reed SI. Association of human cyclin E with aperiodic G1-S phase protein kinase[J]. Science, 1992, 257(5078):1958-1961.
[7] Zschemisch NH, Liedtke C, Dierssen U, et al. Expression of a cyclinE1 isoform in mice is correlated with the quiescent cell cycle status of hepatocytes in vivo[J]. He-patology, 2006, 44(1):164-173.
[8] Leung SY, Ho C, Tu IP, et al. Comprehensive analysis of 19q12 amplicon in human[J]. Mod Pathol, 2006, 19(6):854-863.
[9] MtEumder S, DuPree EL, Almasan A. A dual role of cyclin E in cell proliferation and apoptosis may provide a target for cancer thempy[J]. Curt Cancer Drug Targets, 2004, 4(1):65-75.
[10] 余潇苓, 赵燕娜, 郑智茵, 等. 地西他滨抑制K562白血病细胞增殖和诱导分化的作用[J]. 中国病理生理杂志, 2017, 33(1):13-17.
[11] 王玉茹, 尹利明, 魏克民, 等. 黄芪注射液对白血病K562细胞诱导分化作用的研究[J]. 中国中医药科技, 2013, 20(2):146-148.
[12] 柯大智, 王红宁, 陈地龙, 等. 人参皂苷Rg1抑制白血病细胞K562增殖并诱导分化的分子机制[J]. 第三军医大学学报, 2014, 36(2):125-129.
[13] Squires MS, Feltell RE, Wallis NG, et al. Biological characterization of AT7519 a small-molecule inhibitor of cyclin-dependent kinases in human tumor celllines[J]. Mol Cancer Ther, 2009, 8(12):324-332.
[14] van Riggelen J, Felsher DW. Myc and a Cdk2 senescence switch[J]. Nat Cell Biol, 2010, 12(1):7-9.
[15] Xu L, Wang C, Wen Z, et al. Selective up-regulation of CDK2 is critical for TLR9 signaling stimulated proliferation of human lung cancer cell[J]. Immunol Lett, 2010, 127(2):93-99.
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