天然产物研究与开发 ›› 2014, Vol. 26 ›› Issue (3): 329-334.

• 研究论文 • 上一篇    下一篇

姜黄素通过MAPK信号通路诱导人肝癌SMMC-7721细胞凋亡

李会宣1,杨虹1,张红兵1,高健2*   

  1. 1 河北经贸大学生物科学与工程学院,石家庄 050061;2 华北制药集团新药研究开发有限责任公司 抗体药物研制国家重点实验室,石家庄050015
  • 出版日期:2014-03-29 发布日期:2014-12-08

Curcumin Induces Apoptosis of Human Hepatoma SMMC-7721 Cells via MAPK Signaling Pathway

LI Hui-xuan1, YANG Hong1, ZHANG Hong-bing1, GAO Jian2*   

  1. 1 College of Biology Science and Engineering,Hebei University of Economics and Business,Shijiazhuang 050061,China; 2 State Key Laboratory of Antibody Research & Development,NCPC New Drug R&D Co.,Ltd,Shijiazhuang 050015,China
  • Online:2014-03-29 Published:2014-12-08

摘要: 本文阐述了姜黄素(Curcumin)对体外培养的人肝癌SMMC-7721细胞增殖和凋亡的影响,并探讨了其诱导凋亡的信号转导机制。采用MTT法和细胞计数法检测不同浓度姜黄素对人肝癌细胞株SMMC-7721增殖的影响,利用流式细胞术检测姜黄素对人肝癌SMMC-7721细胞凋亡的影响,通过RT-PCR及Western blot检测姜黄素对人肝癌SMMC-7721细胞中凋亡相关蛋白Caspase-3、Survivin、Bcl-2和Bax表达的影响,最后通过检测MAPK的磷酸化水平分析姜黄素诱导SMMC-7721细胞凋亡的信号转导机制,通过MAPK抑制剂实验进一步证实诱导凋亡的分子机制。研究结果显示,姜黄素呈时间和剂量依赖性抑制人肝癌SMMC-7721细胞的增殖,其中40 μmol/L姜黄素可明显诱导SMMC-7721细胞的凋亡,并呈时间依赖性上调促凋亡蛋白Caspase-3和Bax的表达、下调抗凋亡蛋白Survivin和Bcl-2的表达,姜黄素对凋亡相关蛋白表达的调节及诱导凋亡可以通过激活JNK、抑制ERK和p38 MAPK信号通路实现。表明姜黄素可诱导人肝癌SMMC-7721细胞凋亡,其机制与姜黄素激活JNK、抑制ERK和p38 MAPK信号通路从而上调Caspase-3和Bax的表达,下调Survivin和Bcl-2的表达有关。

关键词: 姜黄素, 人肝癌细胞, 凋亡相关蛋白, MAPK信号通路

Abstract: In this study,the effects of curcumin on proliferation and apoptosis of human hepatoma SMMC-7721 cells were investigated.The possible mechanism of apoptosis was further explored.MTT and cell number assays were used to detect the effect of curcumin on human hepatoma SMMC-7721 cells proliferation.The apoptotic SMMC-7721 cells were examined by flow cytometry.The relative apoptotic protein expressions of Caspase-3,Survivin,Bcl-2 and Bax were detected by RT-PCR and western blot.The possible mechanism of apoptosis was investigated by detecting the phosphorylation of MAPK in SMMC-7721 cells treated with curcumin.MAPK inhibitors were used to further confirm the molecular mechanism of curcumin induced SMMC-7721 cells apoptosis.MTT and cell number assays showed that curcumin inhibited the proliferation of SMMC-7721 cells in a time and dose-dependent manner.Flow cytometry indicated that 40 μmol/L curcumin significantly induced apoptosis of SMMC-7721 cells.RT-PCR and western blot showed that curcumin increased pro-apoptotic protein expression of Caspase-3 and Bax,decreased anti-apoptotic protein expression of Survivin and Bcl-2 in a time-dependent manner.The phosphorylation level of MAPK suggested that curcumin activated JNK and inhibited ERK/P38 MAPK signaling pathways,which mediated modulation of apoptosis-related protein expression and apoptosis of human hepatoma SMMC-7721 cells.Hence,it was concluded that curcumin induced apoptosis through activating JNK and inhibiting ERK/P38 MAPK signaling pathways in human hepatoma SMMC-7721 cells,which involved up-regulating pro-apoptotic protein expression and down-regulating anti-apoptotic protein expression.

Key words: curcumin, human hepatoma cells, apoptosis-related protein, MAPK signaling pathway

中图分类号: 

R285.5 R256.49 R735.7