Erk信号传导通路在雷公藤甲素诱导人乳腺癌MCF-7细胞自噬与凋亡中的影响

目的：探讨雷公藤甲素通过Erk信号传导通路对人乳腺癌细胞MCF-7增殖、自噬和凋亡的影响。方法：培养MCF-7细胞，MTT法检测细胞存活率，Western-blot方法分析凋亡相关蛋白Bax、Bcl-2和Caspase-3，自噬相关蛋白LC3B、p62和Beclin-1和有关MAPK信号通路p38和Erk1/2蛋白水平的变化。结果：10 nmol·L^-1雷公藤甲素显著抑制人乳腺癌细胞MCF-7的增殖，促进凋亡，且呈剂量-时间依赖性；TPI能够增加LC3BⅡ和Beclin-1的表达，降低p62的蛋白水平，诱导MCF-7细胞自噬。雷公藤甲素促进p38和Erk1/2磷酸化，当联用自噬抑制剂时，磷酸化水平下降。结论：雷公藤甲素能够显著抑制人乳腺癌细胞MCF-7增殖，促进凋亡，通过诱导细胞自噬及促进p38及Erk1/2磷酸化等多途径发挥抗肿瘤作用，并首次证明其自噬的发生可能与Erk1/2的激活有关。

Effects of Erk signal transduction pathway in triptolide induced autophagy and apoptosis of human breast cancer MCF-7 cells

OBJECTIVE To investigate the effects of triptolide (TPI) on proliferation,autophagy and death of human breast cancer MCF-7 cells.METHODS MTT assay was used to study the viability of MCF-7 cells under differentconditions.Western-blot was performed to analyze the levels of apoptosisrelated protein,autophagyrelated protein and MAPK signal path related protein,such as Bax,Bcl-2,Caspase-3,LC3B,p62,Beclin-1,p38 and Erk1/2.RESULTS 10 nmol·L^-1 TPI inhibited the proliferation and viability rate of MCF-7 significantly in a timedose dependent manner.TPI induced autophagy by upregulating LC3BⅡ and Beclin-1,and reducing p62 protein level.p38 and Erk 1/2 phosphorylation were promoted by TPI,and inhibited when autophagy inhibition agent was combined.CONCLUSION TPI affects the proliferation and apoptosis of MCF-7 cells,which may be concerned with autophagy and p38/Erk phosphorylation.