组蛋白去乙酰化转移酶抑制剂MS-275对胃癌细胞增殖的影响

Effect of histone deacetylase inhibitor MS-275 in vitro on proliferation of gastric cancer

目的:探讨组蛋白去乙酰化转移酶抑制剂MS-275对胃癌细胞(MKN-45)和人正常胃黏膜细胞(GES-1)及张氏肝细胞(changliver)生长及凋亡的影响。方法:用不同浓度的MS-275分别处理体外培养的胃癌细胞和人正常胃黏膜细胞及张氏肝细胞,用水溶性四唑盐(WST-1)法检测对细胞的增殖抑制作用;流式细胞仪和TUNEL法检测细胞凋亡情况。结果:MS-275可明显抑制胃癌细胞的生长且呈时间和浓度依赖性,细胞凋亡率明显增加,但对正常细胞没有促凋亡作用。低浓度的MS-275能诱导MKN-45细胞发生G0/G1期阻滞,随着药物处理时间的延长,可以明显检测到G0/G1期比例增大。结论:去乙酰化转移酶抑制剂MS-275对胃癌细胞MKN-45具有选择性细胞毒作用,为其临床应用提供了有价值的实验依据,有望成为新的抗胃癌药物。

Objective：To investigate the effects of histone deacetylase inhibitor MS-275 on the proliferation and apoptosis of MKN-45,GES-1 and changliver.Methods：Cultured cells MKN-45,GES-1 and changliver were exposed to different concentrations of MS-275 for different durations and the growth inhibition was evaluated by WST-1 assay.The cell apoptosis was detected by AnnexinV,PI-labeled flow cytometry and TUNEL assay.Results： MS-275 can selectively induced cell death in MKN-45 cell lines in a concentration and time dependent manner,but had no evident effect on normal cell lines.It can be detected that the cell cycle was arrested at G1/S checkpoint after the exposure to lower concentration of MS-275.Conclusion：MS-275 can selectively induce gastric cancer cells death,and provide a valuable research basis for clinical application.The results of this study suggest that histone deacetylase inhibitors are hopeful to become new effective drugs to treat gastric cancer.