端粒酶活性对HeLa细胞生长及化疗敏感性的影响

Effects of Telomerase Activity on Cell Proliferation and Chemosensitivity in Cervix Cancer

目的研究抑制端粒酶活性对HeLa细胞在体内外生长和对顺铂敏感性的影响。方法将野生型端粒酶逆转录酶、端粒酶逆转录酶显性负突变体和对照质粒电转染于HeLa细胞中,绘制细胞生长曲线,四甲基偶氮唑蓝法(MTT)检测细胞对顺铂的敏感性,磷脂酰丝氨酸外翻分析(Annexin V)法检测细胞凋亡情况;接种裸鼠观察其致瘤性及对顺铂敏感性的影响。结果端粒酶逆转录酶显性负突变体转染于HeLa细胞后,端粒酶活性显著下降,细胞生长速度延缓,显著增强顺铂诱导的凋亡,端粒酶活性抑制后对裸鼠致瘤性丧失,而端粒酶活性增强后顺铂对肿瘤的抑制作用下降。结论端粒酶活性下降能抑制HeLa细胞生长,增强顺铂的杀伤作用,反之端粒酶活性升高将导致对顺铂耐药。

Objective To investigate the effects of telomerase activity on cell proliferation and cytotoxicity of cisplatin in cervix cancer. Methods WT-hTERT, DN-hTERT and control plasmid were electroperated into HeLa cells. Cell growth curves were made by cell counting and cell viability was examined by MTT assay. Annexin V/PI double staining was adopted to confirm apoptosis after treated with cisplatin. Tumorigenicity was evaluated by xenografts. Results After HeLa cells were transfected with DN-hTERT, telomerase activity was inhibited, cell growth slowed down, and cisplatin-induced apoptosis obviously enhanced. The inhibition of telomerase activity resulted in loss of tumorigenicity, while the increased telomerase activity lowered the inhibition rate of cisplatin to tumor. Conclusion Decreased telomerase activity could inhibit cell proliferation and enhance cytotoxicity of cisplatin in cervix cancer. Elevated telomerase activity confers resistance to cisplatin.