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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个碱基硫代磷酸修饰的反义寡核苷酸CAGTTAGGGTTAG导入胃癌细胞SGC790 1,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对端粒酶活性抑制作用不同 ,而且有时间依赖趋势。hTR反义PS ODN可增加ADR和DDP抑制胃癌细胞系SGC790 1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SGC790 1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。
Objective To investigate the changes of sensitivity of gastric cancer cells to cisplatin (DDP) and doxorubicin (ADM) after the antisense nucleic acid of thio-modified human telomerase RNA (hTR) was used. Methods A 13 base phosphorothioate modified antisense oligonucleotide CAGTTAGGGTTAG designed for hTR template region was introduced into gastric cancer cell SGC7901 by liposome. MTT assay, And TRAP PCR ELISA assay of the combination of chemotherapy drugs on cell proliferation, apoptosis and telomerase activity. Results The chemotherapeutic drugs ADM and DDP had different inhibitory effects on telomerase activity, and had a time-dependent tendency. hTR Antisense PS ODN can increase the inhibitory effect of ADR and DDP on the telomerase activity of gastric cancer cell line SGC7901, induce apoptosis and inhibit cell proliferation. CONCLUSION: hTR antisense PS ODN can increase the sensitivity of gastric cancer cell line SGC790 1 to chemotherapeutic drugs ADR and DDP in vitro. The mechanism may be related to the inhibition of telomerase activity and induction of apoptosis.