白藜芦醇通过激活p38-p53通路诱导人乳腺癌MCF-7细胞凋亡
Involvement of p38-p53 signal pathway in resveratrol-induced apoptosis in MCF-7 cells
张亚宏 1郭敬功 2郭子华 3谢松强4
作者信息
- 1. 河南大学天然药物与免疫工程重点实验室,河南开封475004
- 2. 河南大学植物逆境生物学重点实验室,河南开封475004
- 3. 开封市中医院脑病科,河南开封475000
- 4. 河南大学天然药物与免疫工程重点实验室,河南开封475004;河南大学化学生物学研究所,河南开封475004
- 折叠
摘要
本研究探讨了白藜芦醇(resveratrol,RSV)诱导人乳腺癌MCF-7细胞凋亡及其作用机制.以MTT法检测白藜芦醇对MCF-7的细胞毒性；应用Hoechst 33258染色观察细胞凋亡的形态学变化；采用流式细胞术检测细胞的凋亡率；以Western blotting检测相关蛋白的表达.结果表明,白藜芦醇可以时间和剂量依赖性地抑制MCF-7细胞的生长;60 μmol·L-1白藜芦醇作用于MCF-7细胞48 h后可使细胞核皱缩、染色质凝聚,并形成明显的凋亡小体；白藜芦醇可以时间依赖性地诱导MCF-7细胞凋亡及p38和p53蛋白的活化.p38 MAPK抑制剂SB203580和p53抑制剂pifithrin-α可以显著降低白藜芦醇诱导的MCF-7细胞的生长抑制率和凋亡率；并且SB203580可以下调由白藜芦醇引起的p53的活化,而pifithrin-α对白藜芦醇引起p38的活化无影响.研究表明,白藜芦醇可以通过激活p38-p53信号通路诱导MCF-7细胞发生凋亡.
Abstract
This paper is to report the study of resveratrol-induced apoptosis and its mechanisms in MCF-7 cells. MTT assay was performed to assess the cytotoxicity of resveratrol on MCF-7 cells. Hoechst 33258 staining was used to observe cellular morphologic changes in apoptosis. Apoptosis was measured by flow cytometric analysis and the protein expression was examined by Western blotting analysis. The results indicated that resveratrol could inhibit MCF-7 cell growth in a time- and concentration-dependent manner. Remarkable morphologic changes in the cells after 60 umolLT1 resveratrol treatment, including cell nuclear shrinkage, DNA condensation and apoptotic bodies, were observed by Hoechst 33258 staining. Resveratrol could induce apoptosis and activate p38 and p53 in a time dependent manner in MCF-7 cells. In addition, the cell growth inhibitory ratio and the apoptotic ratio of resveratrol-treated group decreased markedly by the p38 MAPK inhibitor SB203580 or p53 inhibitor pifithrin-a. Further experiments confirmed that resveratrol-induced p53 activation was reduced by SB203580 whereas the activation of p38 was not affected by pifithrin-a. In conclusion, resveratrol induced apoptosis in MCF-7 cells could be through activating p38-p53 signal pathway.
关键词
白藜芦醇/细胞凋亡/人乳腺癌MCF-7细胞/p38/p53Key words
resveratrol/apoptosis/MCF-7 cell/p38/p53引用本文复制引用
基金项目
中国博士后科学基金(20100470995)
出版年
2011
NETL
NSTL
维普
万方数据