Background: Hepatocellular carcinoma (HCC) has high mortality partly due to acquiring drug resistance during chemotherapy
treatment. Therefore, it is necessary to explore the underlying mechanism of drug resistance.
Methods: We used 2-DE and MALDI-TOF-MS analysis to explore the possible molecular insight into 5-FU resistance in HCC. The differentially
expressed proteins were validated by Western blot analysis.
Results: We identified 102 unique proteins including p16, maspin, PRDX6, PSMB7, MYL6, PHB, and HSP27 with alteration in SMMC-
7721/5-FU. Furthermore, down-regulation of PRDX6 and PSMB7 enhanced SMMC-7721/5-FU cells to 5-FU sensitivity.
Conclusions: Our study suggests that targeting drug resistant genes such as PRDX6 and PSMB7 could be a novel approach to overcome
5-FU resistance in HCC cells.