硫代修饰端粒酶反义核酸联合顺铂、阿霉素对胃癌细胞作用的研究

目的：探讨应用硫代修饰人端粒酶RNA（hTR)反义核酸后胃癌细胞对顺铂（DDP）和阿霉素（ADM）敏感性的变化。方法：采用脂质体将针对hTR模版区设计的13相碱基硫代磷酸修饰的反义寡核苷酸CAGTTAGGGTTAG导入胃癌细胞SGC7901，应用四甲基偶氮唑蓝（MTT）法，流式细胞仪和TRAP－PCR－ELISA法测定联合应用化疗药后对细胞增殖，凋亡和端粒酶活性的影响。结果：化疗药物ADM和DDP地端粒酶活性抑制作用不同，而且有明显依赖趋势。hTR反义PS－ODN可增加ADR和DDP抑制胃癌细胞系SGC7901端粒酶活性，诱导细胞凋亡和抑制细胞增殖的作用。结论：hTR反义PS－ODN在体外能增加胃癌细胞系SGC701对化疗药ADR、DDP敏感性，其机制可能与其抑制细胞端粒酶活性，诱导细胞凋亡有关。

The effect of hTR antisense PS-ODN in combination with cisplatin and adriamycin on human gastric cancer cell line

Objective To study the effect of hTR antisense PS-ODN on the susceptibility of human gastric cancer cell line SGC7901 to Adriamycin and Cisplatin. Methods hTR antisense PS-ODN with sequence CAG-TTAGGGTTAG which can recognize the RNA template of telomerase was transfected into SGC7901 by lipofectamine, and drug sensitivity test was performed with MTT method, telomerase activity was quantitatively measured by TRAP-PCR-ELISA methods, the apoptotic cells were measured with FCM. Results The telomerase activity in gastric cancer cell line SGC7901 after treatment with cisplatin and doxorubicin was different, and the change of telomerase activity of SGC7901 by cisplatin and doxorubicin was in time-dependent manner. The inhibitory ability of cisplatin and doxorubicin combined with hTR antisense PS-ODN in cell line SGC7901 was higher than that of these drugs used alone. Telomerase activity was dramatically declined during the cell incubation with hTR antisense PS-ODN combined with ADM or DDP. The hTR antisense PS-ODN increased susceptibility to cisplatin or doxorubicin-induced apoptotic cell death in gastric cancer cell line SGC7901. Conclusions The hTR antisense PS-ODN increased susceptibility to cisplatin or doxorubicin in gastric cancer cell line. This may be correlated with its inhibitory effects on telomerase activity and the ability of induced apoptotic cell death. These findings indicate that hTR antisense PS-ODN may represent a novel chemosensitive agent.