摘要
目的观察AZD2281对乳腺癌MDA-MB-231细胞株增殖和凋亡的影响,并探讨其可能的机制。方法 MTT法和流式细胞仪法观察不同浓度AZD2281(2.5、5、10 nmol/L)作用于MDA-MB-231细胞24、48、72 h后对细胞增殖、周期分布及细胞凋亡的影响;Western blotting检测经AZD2281处理该细胞24 h后细胞凋亡相关蛋白Bcl-2和caspase-3表达水平的变化。结果 AZD2281可显著抑制MDA-MB-231细胞增殖,且呈时间和剂量依赖性;AZD2281作用于MDA-MB-231细胞24 h后,细胞被阻滞在G0/G1期,并促进其凋亡,且呈剂量依赖性。AZD2281作用MDA-MB-231细胞24 h后,凋亡抑制蛋白Bcl-2的表达呈剂量依赖性下降,而凋亡促进蛋白caspase-3的表达呈剂量依赖性上升。结论 AZD2281能显著抑制MDA-MB-231细胞增殖和促进其凋亡,其作用机制可能是通过上调caspase-3和下调Bcl-2蛋白表达实现的。
Objective To investigate the effects of AZD2281 on proliferation and apoptosis of human breast cancer cell MDA- MB-231 in vitro and the possible mechanisms. Methods Different concentrations of AZD2281 （2. 5, 5, 10 nmol/L） were used to treat MDA-MB-231 cells for 24,48,72 h, and its effects of time and dose were observed. Cell proliferation inhibition rates were measured by MTr assay. The flow cytometry was used to analyze cell-cycle distribution and cell apoptosis. The western blotting was used to detect the expression levels of Bcl-2 and caspase-3. Results The proliferation of MDA-MB-231 cells was inhibited by AZD2281 in a dose-and time-dependent manner. The cell was arrested in the G0/G1 phase by AZD2281 treatment after 24 h, and the cell apoptosis was induced in a dose-dependent manner. AZD2281 could down-regulate the protein expression of Bcl-2 level after treatment with AZD2281 but up- regulate the protein expression level of caspase-3 protein. Conclusion AZD2281 can inhibit the proliferation of human breast cancer cell MDA-MB-231 and induce its apoptosis by down-regulating the expression of Bcl-2 protein and up-regulating the expression of caspase-3 protein.
出处
《临床肿瘤学杂志》
CAS
2015年第7期593-597,共5页
Chinese Clinical Oncology
