摘要
目的:探究荜茇酰胺对乳腺癌细胞MDA-MB-231、MCF-7和正常乳腺细胞MCF-10A增殖、凋亡和细胞周期的影响及其潜在的分子机制.方法:采用不同浓度荜茇酰胺干预MDA-MB-231、MCF-7、MCF-10A细胞,MTT法检测细胞增殖能力;细胞克隆形成法检测细胞克隆形成能力;流式细胞术检测细胞凋亡和细胞周期;Western Blot检测细胞中 cleaved Caspase-3、Bcl-2、Bax、Cyclin D1、p53、p-JAK2、p-STAT3、HIF-1α、Survivin 蛋白表达.结果:荜茇酰胺可呈浓度依赖性抑制MDA-MB-231、MCF-7细胞增殖并诱导其凋亡,而对MCF-10A细胞无明显抑制作用;荜茇酰胺可下调 MDA-MB-231 细胞 p53、Bcl-2、Cyclin D1、p-STAT3、Survivin、HIF-1α 及 MCF-7 细胞 p53、p-STAT3、Survivin、HIF-1α蛋白表达,上调MDA-MB-231细胞cleaved Caspase-3、Bax蛋白表达.结论:荜茇酰胺能抑制乳腺癌细胞MDA-MB-231、MCF-7增殖并诱导其凋亡,其机制可能与负向调控STAT3/HIF-1α通路有关.
Abstract
Objective:To investigate the effect of piperlongumine on the proliferation,apoptosis and cell cycle of breast cancer cells MDA-MB-231,MCF-7 and normal breast cells MCF-10A and its potential molecular mechanism.Methods:MDA-MB-231,MCF-7 and MCF-10A cells were treated with different concentrations of piperlongumine,and the cell proliferation was detected by MTT assay.Cell clone formation assay was used to detect cell clone formation ability.Flow cytometry was used to detect cell apoptosis and cell cycle.The protein expressions of cleaved Caspase-3,Bcl-2,Bax,Cyclin D1,p53,p-JAK2,p-STAT3,HIF-1α and Survivin were detected by Western Blot.Results:Piperlongumine inhibited the proliferation and induced apoptosis of MDA-MB-231 and MCF-7 cells in a dose-dependent manner,but had no obvious inhibitory effect on MCF-10A cells.The protein expressions of p53,Bcl-2,Cyclin D1,p-STAT3,Survivin,HIF-1α in MDA-MB-231 cells and p53,p-STAT3,Survivin,HIF-1α in MCF-7 cells were down-regulated and cleaved Caspase-3 and Bax protein expressions in MDA-MB-231 cells were up-regulated.Conclusion:Piperlongumine can inhibit the proliferation and induce apoptosis of breast cancer cells MDA-MB-231 and MCF-7,the mechanism may be related to the negative regulation of STAT3/HIF-1α pathway.
基金项目
陕西省科技发展计划(2024JC-YBMS-618)
西安医学院博士科研启动基金(2021DOC05)
西安医学院科技能力提升计划(2022NLTS025)