YM155对人胃癌细胞株MKN28的作用及其机制研究

Effect and Mechanism of YM155 on Human Gastric Carcinoma Cell Line MKN28

背景:研究发现生存素(survivin)在胃癌组织中高表达,YM155是survivin的特异性抑制剂。目的:探讨YM155对人胃癌细胞株MKN28的作用及其机制。方法:以不同浓度YM155作用于人胃癌细胞株MKN28。采用甲基噻唑基四唑(MTT)法检测细胞增殖抑制率;以原位末端标记(TUNEL法)检测细胞凋亡率;以逆转录聚合酶链反应(RTPCR)、蛋白质印迹法分别检测survivin mRNA和survivin、多聚ADP核糖聚合酶(PARP)、caspase-3蛋白表达。结果:YM155作用后,MKN28细胞增殖抑制,凋亡增加。随着YM155浓度升高,survivin mRNA和蛋白表达水平明显降低,并伴随PARP、caspase-3蛋白裂解。结论:YM155可抑制人胃癌细胞株MKN28增殖,并诱导其凋亡,此机制可能与抑制survivin表达,继而激活caspase凋亡信号通路有关。

It has been reported that survivin is over-expressed in human gastric cancer tissue. YM155 is the specific inhibitor of survivin. Aims： To investigate the effect and mechanism of YM155 on human gastric carcinoma cell line MKN28. Methods： Gastric carcinoma cell line MKN28 was treated with different concentrations of YM155. The cell proliferation inhibition rate was measured by methyl thiazolyl tetrazolium （MTT） assay. Cell apoptosis was determined by in situ end-labeling （TUNEL） method. The mRNA expression of survivin and protein expressions of survivin, poly （ADPribose） polymerase （PARP）, and caspase-3 were determined by reverse transcription polymerase chain reaction （RT- PCR） and Western blotting, respectively. Results： The proliferation of MKN28 cells was inhibited and apoptosis was induced by YM155. Furthermore, the survivin mRNA and protein expressions were significantly decreased in MKN28 cells treated by YM155, accompanied by cleavage of PARP and caspase-3. Conclusions： YM155 can inhibit proliferation and induce apoptosis of human gastric carcinoma cell line MKN28, the mechanism may be related to inhibiting the expression of survivin, and resulting in activating the apoptotic signal pathway of caspase.