三氧化二砷诱导HeLa细胞凋亡与其抑制HPV18 E6表达和端粒酶活性有关

目的 探讨三氧化二砷(As2O3)诱导人宫颈癌HeLa细胞凋亡时,对14PV18 E6致瘤基因和端粒酶活性的影响。方法 用不同浓度的As2O3作用于HeLa细胞不同时间段后,光镜和电镜观察细胞形态改变,流式细胞仪检测细胞周期改变,MTT法测定细胞生长抑制情况。RT-PCR方法检测HPV18 E6的表达,TRAP-ELISA方法测定细胞内端粒酶活性变化。结果 2μmol／L As2O3处理HeLa细胞48h后,可降低细胞存活率,诱导细胞凋亡,抑制HPV18 E6的表达,细胞内端粒酶活性明显下降。As2O3对HeLd细胞的这种作用呈时间-剂量依赖关系。结论 As2O3诱导HeLa细胞凋亡可能与其抑制HPV18 E6致瘤基因的表达有关,细胞内端粒酶活性的抑制可能与这种E6致瘤基因的抑制有关。

The association of HeLa cell apoptosis induced by arsenic trioxide with the down-regulation of HPV18 E6 oncogene and inhibition of telomerase activity

OBJECTIVE: To study the effect of As2O3 induction of HeLa cell apoptosis on HPV18 E6 expression and telomerase activity. METHODS: HeLa cells were treated with As2O3 in various concentrations. The effect of As2O3 on HeLa cell survival and apoptosis was determined by MTT assay, light and electron microscopy, and flow cytometry. Telomerase activity in HeLa cells was determined by TRAP-ELISA and the expression of HPV18 E6 mRNA was assayed by RT-PCR. RESULTS: After being treated with 2 micromol/L As2O3 for 48 h, the survival of HeLa cells decreased, and marked apoptosis was observed in a time- and dose-dependent manner. There was a good correlation between cell apoptosis and viral E6 gene expression and inhibition of telomerase activity following As2O3 treatment. CONCLUSION: The molecular mechanisms of As2O3 effect on HeLa cells may be related to down-regulation of HPV18 E6 oncogene expression and inhibition of telomerase activity.