基础医学与临床 ›› 2019, Vol. 39 ›› Issue (4): 581-584.

• 短篇综述 • 上一篇    下一篇

新型靶向药物与PTEN在肝癌中耐药的相关性研究进展

林剑1,张谢2,李宏2   

  1. 1. 宁波大学医学院
    2. 宁波市医疗中心李惠利医院
  • 收稿日期:2018-04-12 修回日期:2018-07-24 出版日期:2019-04-05 发布日期:2019-03-26
  • 通讯作者: 李宏 E-mail:lancet2010@aliyun.com
  • 基金资助:
    浙江省公益技术应用研究计划项目;浙江省医药卫生平台计划项目;宁波市重大民生项目

Research progress in correlation between PTEN and new targeted drug resistance to hepatocellular carcinoma

1, 1,   

  • Received:2018-04-12 Revised:2018-07-24 Online:2019-04-05 Published:2019-03-26

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。索拉菲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菲尼耐药,从而恢复索拉菲尼在肝癌细胞中的敏感性。

关键词: 关键词:磷酸酶及张力蛋白同源物, 索拉菲尼, 耐药, 肝癌

Abstract: 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 lead to drug resistance in the long term. The study shows that sorafenib resistance to hepatocellular carcinoma relates to PTEN regulation, through the down-regulation of PTEN expression, activation of PI3K/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.

Key words: Key word: phosphatase and tensin homologue(PTEN), sorafenib, drug resistance, hepatocellular carcinoma

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