论文部分内容阅读
目的:探讨Mcl-1以及PI3K通路活化对胃癌细胞生长及化疗敏感性的影响。方法:分别用阿霉素、足叶乙甙和PI3K通路抑制剂(wortmannin)在不同时间段处理胃癌细胞BGC-823后,采用四甲基偶氮唑蓝法检测细胞对药物的敏感性,流式细胞仪检测细胞凋亡情况并分析细胞周期,Western blot法测定细胞Mcl-1蛋白活性,RT-PCR法测定细胞Mcl-1 mRNA活性。结果:阿霉素、足叶乙甙作用BGC-823 24 h后,Mcl-1蛋白活性降低,Mcl-1 mRNA表达下降。加用Wortmannin后,阿霉素、足叶乙甙对BGC-823凋亡诱导和周期阻滞作用持续增强,Mcl-1蛋白及mRNA表达进一步降低,肿瘤细胞对药物保持较高敏感性。结论:阿霉素、足叶乙甙至少部分是通过下调Mcl-1的表达诱导胃癌细胞凋亡。Mcl-1、PI3K通路活化可促进胃癌细胞的生存,降低化疗敏感性。
Objective: To investigate the effects of Mcl-1 and PI3K activation on gastric cancer cell growth and chemosensitivity. Methods: After treating gastric cancer cells BGC-823 with doxorubicin, etoposide and PI3K pathway inhibitor (wortmannin) at different time points, the sensitivity of the cells to the drug was measured by MTT assay Cytometry was used to detect cell apoptosis and cell cycle analysis. Western blot was used to detect the activity of Mcl-1 protein. Mcl-1 mRNA was detected by RT-PCR. RESULTS: After doxorubicin and etoposide administered BGC-823 for 24 h, the activity of Mcl-1 protein decreased and the expression of Mcl-1 mRNA decreased. After addition of Wortmannin, the effects of doxorubicin and etoposide on apoptosis induction and cycle arrest of BGC-823 cells continued to increase, while the expression of Mcl-1 protein and mRNA was further decreased. The tumor cells remained highly sensitive to the drugs. CONCLUSION: Adriamycin and etoposide induce gastric cancer cell apoptosis at least in part by down-regulating Mcl-1 expression. Mcl-1, PI3K pathway activation can promote the survival of gastric cancer cells, reduce the sensitivity of chemotherapy.