CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivo

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• 作者：Xing-Xing He ; Yu-Nan Zhang ; Jun-Wei Yan ; Jing-Jun Yan ; Qian Wu ; Yu-Hu Song
• 刊名：Tumor Biology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：37
• 期：1
• 页码：807-815
• 全文大小：960 KB
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380
• 卷排序：37

文摘

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.Keywordsp53Hepatocellular carcinomaCP-31398Therapy