摘要
目的探讨甲基莲心碱(Nef)对人肝癌细胞索拉非尼(SORA)耐药的逆转作用及其对PI3K-Akt通路的影响。方法将人肝癌耐药细胞株HepG2/SORA随机分为空白对照组、SORA组、Nef组、SORA+Nef联合组,每组设置6个复孔。细胞融合度达80%左右时,各组培养基中加入药物,空白对照组加入等体积细胞培养基,培养56 h。检测HepG2/SORA细胞的增殖、凋亡情况及p-Akt、Akt蛋白表达水平。结果SORA组、Nef组和SORA+Nef联合组细胞凋亡率显著高于空白对照组(P<0.05),SORA+Nef联合组细胞凋亡率显著高于SORA组、Nef组(P<0.05)。SORA组、Nef组和Nef+SORA组细胞增殖抑制率显著高于空白对照组(P<0.05);SORA+Nef联合组细胞增殖抑制率显著高于Nef组(P<0.05)。SORA联合Nef能显著降低p-Akt及Akt的表达,而SORA组中p-Akt及Akt的表达高于空白对照组及Nef组。结论Nef可逆转HepG2/SORA对SORA的耐药,其机制可能与阻断PI3K-Akt信号通路,降低p-Akt、Akt蛋白表达水平,从而与SORA产生协同作用有关。
Objective To investigate the reversal effect of neferine(Nef)on the sorafenib(SORA)resistance in human hepatoma cells and its effect on PI3K-Akt pathway.Methods Human hepatoma drug-resistant cell line,HepG2/SORA was randomly divided into the blank control group,the SORA group,the Nef group,and the SORA+Nef combination group,with 6 replicate wells in each group.When the degree of cell fusion reached about 80%,drugs were added to the culture medium of each group,and equal volume cell culture medium was added in the blank control group for 56 h of cultivation.The proliferation and apoptosis of HepG2/SORA cells and the expression levels of p-Akt and Akt proteins were detected.Results The apoptosis rate of the SORA group,the Nef group,and the SORA+Nef combination group was significantly higher than that of the blank control group(P<0.05),and the apoptosis rate of the SORA+Nef combination group was significantly higher than that of the SORA group and Nef group(P<0.05).The cell proliferation inhibition rate of the SORA group,the Nef group,and the SORA+Nef group was significantly higher than that of the blank control group(P<0.05);the cell proliferation inhibition rate of the SORA+Nef combination group was significantly higher than that of the Nef group(P<0.05).SORA combined with Nef significantly decreased the expression of p-Akt and Akt,and the expression of p-Akt and Akt in SORA group was higher than that in blank group and Nef group.Conclusion Nef can reverse the SORA resistance in HepG2/SORA,and the mechanism may be related to blocking PI3K-Akt signaling pathway and reducing the expression levels of p-Akt and Akt proteins,so as to exert a synergistic effect wit h SORA.
作者
易晓雷
肖浩
李旭辉
刘志鹏
谢明
YI Xiaolei;XIAO Hao;LI Xuhui;LIU Zhipeng;XIE Ming(Department of Hepatopancreatobiliary and Vascular Surgery,Changsha Hospital of Traditional Chinese Medicine(Changsha No.8 Hospital),Hunan,Changsha 410100,China)
出处
《中国医药科学》
2022年第21期28-31,共4页
China Medicine And Pharmacy
基金
湖南省卫生计生委科研计划课题项目(B20180799)。
