The
tumor suppressor p53 is one of the most frequently mutated genes in
hepatocellular carcinoma (HCC). Previous studies demonstrated that
CP-31398 restored the native conformation of mutant p53 and trans-activated p53 downstream genes in
tumor cells. However, the research on the application of
CP-31398 to
liver cancer has not been reported. Here, we investigated the effects of
CP-31398 on the phenotype of HCC cells carrying p53 mutation. The effects of
CP-31398 on the characteristic of p53-mutated HCC cells were evaluated through analyzing cell cycle, cell apoptosis, cell proliferation, and the expression of p53 downstream genes. In
tumor xenografts developed by PLC/PRF/5 cells, the inhibition of
tumor growth by
CP-31398 was analyzed through gross morphology, growth curve, and the expression of p53-related genes. Firstly, we demonstrated that
CP-31398 inhibited the growth of p53-mutated
liver cancer cells in a dose-dependent and p53-dependent manner. Then, further study showed that
CP-31398 re-activated wild-type p53 function in p53-mutated HCC cells, which resulted in inhibitive response of cell proliferation and an induction of cell-cycle arrest and apoptosis. Finally, in vivo data confirmed that
CP-31398 blocked the growth of xenografts
tumors through transactivation of p53-responsive downstream molecules. Our results demonstrated that
CP-31398 induced desired phenotypic change of p53-mutated HCC cells in vitro and in vivo, which revealed that
CP-31398 would be developed as a therapeutic candidate for HCC carrying p53 mutation.