AZD5363抑制乳腺癌MDA-MB-231细胞增殖和迁移并诱导细胞凋亡  

AZD5363 inhibits cell proliferation,migration and induces apoptosis of breast cancer MDA-MB-231 cells

作　　者：李若彤[1] 崔海娟[2] 王凤泽[3] 于爱莲[4] 秦树存[5] 王学春[4] 

机构地区：[1]新泰市人民医院病理科,山东新泰271200 [2]泰山医学院护理学院,山东泰安271000 [3]泰山医学院生命科学学院,山东泰安271000 [4]泰山医学院基础医学院,山东泰安271000 [5]泰山医学院动脉粥样硬化研究所山东省高校动脉粥样硬化重点实验室,山东泰安271000

出　　处：《肿瘤》2017年第8期824-830,共7页Tumor

摘　　要：目的:探讨蛋白激酶B(又称Akt)抑制剂AZD5363对人乳腺癌MDAMB-231细胞增殖、迁移和凋亡的影响,并探讨其可能的分子作用机制。方法:用不同浓度(0.5、1、5、10、20和50μmol/L)的AZD5363处理MDA-MB-231细胞后,采用MTT法检测细胞增殖活力,FCM法分析细胞周期的变化,划痕愈合实验和Transwell小室法检测细胞迁移能力的变化,TUNEL法测定细胞凋亡率,蛋白质印迹法检测细胞周期和凋亡相关蛋白的表达水平变化。结果:AZD5363可抑制MDA-MB-231细胞的增殖活力(P<0.05),并呈剂量依赖性;AZD5363可通过上调p53表达和下调cyclin B1表达(P值均<0.05),阻滞细胞周期于S期(P<0.05)。AZD5363能够明显抑制MDAMB-231细胞的迁移(P<0.05),同时诱导MDA-MB-231细胞发生凋亡(P<0.05),其分子机制可能与AZD5363促进caspase-3和多聚ADP-核糖聚合酶[poly(ADP-ribose)polymerase,PARP]的剪切活化相关(P值均<0.05)。结论:AZD5363能够抑制细胞增殖和迁移,同时诱导MDA-MB-231细胞凋亡,从而表现出抗肿瘤活性。Objective： To investigate the effects of AZD5363, an inhibitor of protein kinase B （Akt）, on proliferation, migration and apoptosis of human breast cancer cell line MDA-MB-231, and to further clarify their possible molecular mechanisms Methods： After treatment with different concentrations （0.5, 1, 5, 1 0, 20 and 50 μmol/L） of AZD5363, the viability of MDA-MB-231 cells was detected by MTT assay, the cell cycle distribution was analyzedby FCM, the cell migration ability was detected by wound healing test and Transwell chamber assay, the cell apoptosis rate was detected by TUNEL method. Then the expression levels of cell cycle- and apoptosis-related proteins were measured by Western blotting. Results： AZD5363 suppressed the cell viability in a dose-dependent manner （P 〈 0.05）, and arrested the cell cycle progression at S phase by up-regulating the expression of p53 and down-regulating the expression of cyclin B1 （all P 〈 0.05）. AZD5363 significantly inhibited the cell migration （P 〈 0.05）, and induced the cell apoptosis （P 〈 0.05） by activating caspase-3 and poly （ADP-ribose） polymerase （PARP） proteins （both P 〈 0.05）.Conclusion; AZD5363 can inhibit cell activity and migration, and induce apoptosis of human breast cancer cell line MDA-MB-231, thereby exhibiting its anticancer activity.

关 键 词：乳腺肿瘤 蛋白激酶抑制剂 细胞增殖 细胞迁移分析 细胞凋亡 AZD5363 

分 类 号：R737.9[医药卫生—肿瘤]