索拉菲尼对肝癌HepG2细胞凋亡、耐药及PTEN蛋白表达的影响  

Sorafenib induces apoptosis and drug resistance of HCC cells and regulates PTEN expression

作　　者：祝珊珊 秦飞 陈仲巍 毕丽伟 陈丹 许莉 郑晓辉 ZHU Shan-shan;QIN Fei;CHEN Zhong-wei;BI Li-wei;CHEN Dan;XU Li;ZHENG Xiao-hui(Dept of Pharmacy,Drug Testing Center,Xiamen Medical College,Xiamen 361026,China;Key Lab of Marine Medicinal Natural Products Resources,Xiamen Medical College,Xiamen 361026,China;FuJian Provincial Key Lab of Fuctional and Clinical Transiation Medicine,Xiamen Medical College,Xiamen 361026,China)

机构地区：[1]厦门医学院药学系药物检测中心,福建厦门361026 [2]厦门医学院厦门市海洋药用天然产物资源重点实验室,福建厦门361026 [3]厦门医学院机能与临床转化福建省高校重点实验室,福建厦门361026

出　　处：《中国药理学通报》2020年第11期1532-1536,共5页Chinese Pharmacological Bulletin

基　　金：厦门医学院自然科学科研项目(No K2016-35);福建省中青年教师教育科研项目(No JAT20170699)。

摘　　要：目的探讨索拉菲尼(Sorafenib,So)对肝细胞癌HepG2的毒性作用及其机制。方法不同浓度索拉菲尼作用HepG2细胞,CCK-8法测定细胞活性,结晶紫染色观察;流式细胞术检测细胞凋亡;细胞内蛋白表达采用Western blot检测。结果So剂量依赖地降低HepG2细胞活性并诱导细胞凋亡;Western blot显示So可上调PTEN、Bax蛋白表达,抑制磷酸化AKT、Bcl-2的蛋白以及耐药基因ABCC2和ABCG2蛋白的表达。结论So抑制HepG2细胞存活并诱导凋亡;机制可能与So促进肝癌细胞PTEN以及Bax蛋白表达;抑制Bcl-2以及p-AKT和耐药基因ABCC2、ABCG2的表达有关。Aim To investigate the toxic effect of sorafenib on human hepatocellular cell HepG2 and the relative mechanism.Methods CCK-8 assayed and crystal violet staining photo techniques were used to detected cell viability.Flow cytometry was applied to analyse cell apoptosis.Western blot was employed to detect the protein expression for ABCC2,ABCG2,PTEN,p-AKT,Bax,Bcl-2.Results Sorafenib significantly suppressed cell viability and induced cell apoptosis.The protein expressions of PTEN and Bax were up-regulated,and p-AKT,Bcl-2,ABCC2 and ABCG2 were down-regulated.Conclusions Sorafenib has inhibitory effect on HepG2 cells,and the mechanism of apoptosis may correlate with the up-regulation of PTEN expression and inhibition of p-AKT,ABCC2 and ABCG2.

关 键 词：肝癌细胞 索拉菲尼 细胞增殖 PTEN 细胞凋亡 耐药基因 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R329.25[医药卫生—基础医学]