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    As2O3对乳腺癌细胞的生长及端粒酶活性的影响

    Influence of arsenic trioxide on breast cancer cell and telomerase activity

      摘要
    • 摘要: 目的:探讨不同浓度As2O3对人乳腺癌细胞株MDA-MB-231端粒酶及其亚单位hTERT-mRNA活性表达的影响,为临床治疗乳腺癌提供理论和实验依据。方法:将不同浓度的As2O3与MDA-MB-231细胞共培养不同时间后,MTT比色法检测As2O3对MDA-MB-231细胞的生长抑制作用;TRAP-PAGE-银染法检测As2O3作用后细胞端粒酶活性的改变;RT-PCR法测定MDA-MB-231细胞hTERT-mRNA的表达。结果:As2O3可显著抑制MDA-MB-231细胞生长,且存在浓度、时间效应关系,其24 h IC50为24.73μmol/L,48 h IC50为6.99μmol/L;用终浓度分别为10、20、40μmol/L的As2O3与MDA-MB-231细胞作用24h、48 h,银染条带显示出端粒酶活性显著下降;RT-PCR产物电泳条带显示出hTERT-mRNA的表达明显下降。结论:As2O3在体外可显著抑制MDA-MB-231细胞的生长,具有较明显的细胞毒作用;As2O3能显著抑制MDA-MB-231细胞端粒酶及其亚单位端粒酶逆转录酶的活性,且抑制作用具有明显的时间和浓度依赖关系。

       

      Abstract: Objective: To investigate the inhibitary effect of different concentrations of arsenic trioxide(As2O3) on breast cancer cells MDA-MB-231 and on the activity of telomerase hTERT-mRNA so as to provide theoretical and experimental basis for the treatment of breast cancer.Methods: MDA-MB-231 cells were cultured with As2O3 diflerint cokcenfrations.The growth inhibition was analyzed by MTT assay;the telomerase activity was determined by TRAP-PAGE-SILVER staining;the hTERT-mRNA expression was examined by RT-PCR assay.Results: As2O3 could obviously inhibit the growth of MDA-MB-231 cells,which was related with the concentrations of As2O3 and time of culture.Its 24-hour inhibitory concentration(IC50) was 24.73 μmol/L and 48-hour inhibitory concentration(IC50) was 6.99 μmol/L.Treated with As2O3(10-40 μmol/L) for 24-48 h,the telomerase activity and hTERT-mRNA expression of MDA-MB-231 cells were greatly inhibited.Conclusions: As2O3 can inhibit the growth of MDA-MB-231 cells significantly.Treated with As2O3,the activity of telomerase and telomerase hTERT-mRNA can be inhibited remarkably,and the effects are dependent on the concentrations and time of culture.

       

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