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