消瘤1号通过影响bax和bcl-2的表达诱导人乳腺癌细胞MCF-7凋亡

The apoptosis of human breast cancer cells MCF-7 induced by Xiaoliu No.1 compound through influencing the expression of bax and bcl-2

目的:探讨中成药消瘤1号诱导MCF-7人乳腺癌细胞凋亡的作用及其分子机制。方法:采用细胞培养技术,用不同浓度的含药血清(含药物浓度为1、10、100、1 000μg/ml)处理MCF-7细胞,用MTT法检测药物对细胞增殖的影响;以流式细胞仪测定碘化丙啶染色细胞细胞周期的变化;采用实时-PCR法检测bax mRNA和bcl-2 mRNA表达。结果:消瘤1号处理MCF-7细胞后,随着药物浓度增加,作用时间延长,细胞增殖速度减慢。流式细胞仪检测结果显示,消瘤1号使MCF-7细胞阻滞于S期,随着药物浓度的增加,细胞凋亡逐渐增加。消瘤1号还能够促进细胞中bax mRNA表达,减少bcl-2 mRNA表达,并呈浓度依赖性。结论:消瘤1号诱导MCF-7细胞凋亡,其机制涉及bax/bcl-2比值升高,引起线粒体释放细胞色素C。消瘤1号有可能开发为治疗乳腺癌的药物。

Objective：To investigate the inducing effect of Xiaoliu No.1 compound on apoptosis of human breast cancer cell line MCF-7 and explore the possible molecular mechanism.Methods：MCF-7 cells were cultured and treated with serum which contained 1,10,100 and 1 000 μg/ml of the compound and normal saline for 24,48 and 72 h.Changes of cell proliferation were analyzed by MTT assay and alteration of cell cycles were determined by flow cytometry after propidium iodide staining.Expression levels of bax mRNA and bcl-2 mRNA were examined by real time PCR method.Results：The rate of cell proliferation was significantly slowed down by Xiaoliu No.1 compound in a time-and dose-dependent manners.Flow cytometry showed that MCF-7 cells were blocked at S stage after drug treatment.The compound induced apoptosis of MCF-7 cells in a dose-dependent manner.Besides,the expression level of bax mRNA was significantly increased by the compound,while the expression level of bcl-2 mRNA was reduced in a dose-dependent manner.Conclusion：Xiaoliu No.1 compound induces apoptosis of MCF-7 cells by increasing bax/bcl-2 ratio and subsequent release of cytochrome C from the mitochondra.Xiaoliu No.1 compound may be developed as a drug for treating breast cancer.