摘要
PTEN是继p53发现之后第二位最常突变的抑癌基因,其变异或丢失与肝癌发生有着紧密的关系。索拉非尼是FDA批准的口服多激酶抑制剂,是晚期肝癌一线的新型靶向治疗药物,但长期服用可导致耐药。索拉非尼在肝癌中耐药机制研究发现与PTEN靶向作用密切相关,其通过PTEN表达量下调,激活PI3K/Akt信号通路,或微小RNA调控PTEN后表达量降低,从而导致索拉非尼在肝癌中耐药;通过中药提取物、Akt抑制剂等方法间接提高PTEN表达量可以降低索拉非尼耐药,从而恢复索拉非尼在肝癌细胞中的敏感性。
PTEN is the second most frequently mutated tumor suppressor gene following the discovery of p53. PTEN mutation or loss has a close relationship with the occurrence of hepatocellular carcinoma. Sorafenib is an oral multi-kinase inhibitor approved by the FDA. It is a first-line targeted treatment for advanced hepatocellular carcinoma, but it is vulnerable to drug resistance in long term treatment. The study shows that sorafenib resistance to hepatocellular carcinoma relates to PTEN regulation, through the down-regulation of PTEN expression, activation of PI3 K/Akt pathway, or decreased expression of PTEN modulated by microRNAs;extraction from Chinese herbal and Akt inhibitors indirectly increase the expression of PTEN reversing sorafenib resistance, so to recover sensitivity of hepatocellular carcinoma to sorafenib.
作者
林剑
张谢
李宏
LIN Jian;ZHANG Xie;LI Hong(School of Medicine,Ningbo University,Ningbo 315211;Department of Pharmacy,Ningbo Medical Center,Li Huili Hospital,Ningbo 315040;Department of General Surgery,Ningbo Medical Center,Li Huili Hospital,Ningbo 315040,China)
出处
《基础医学与临床》
CSCD
2019年第4期581-584,共4页
Basic and Clinical Medicine
基金
浙江省公益技术应用研究计划项目(2017C35002)
宁波市重大民生项目(2013C51009)
浙江省医药卫生平台计划项目(2016DTA009)
关键词
磷酸酶及张力蛋白同源物
索拉非尼
耐药
肝癌
phosphatase and tensin homologue(PTEN)
sorafenib
drug resistance
hepatocellular carcinoma
