Tumor Biology

, Volume 37, Issue 1, pp 807–815 | Cite as

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

  • Xing-Xing He
  • Yu-Nan Zhang
  • Jun-Wei Yan
  • Jing-Jun Yan
  • Qian Wu
  • Yu-Hu Song
Original Article

Abstract

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.

Keywords

p53 Hepatocellular carcinoma CP-31398 Therapy 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No.81072003, 81270506, 81472832) and the Outstanding Youth Science Foundation of Tongji Hospital (No. YXQN005).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Xing-Xing He
    • 1
    • 2
  • Yu-Nan Zhang
    • 1
  • Jun-Wei Yan
    • 1
  • Jing-Jun Yan
    • 1
  • Qian Wu
    • 1
  • Yu-Hu Song
    • 2
  1. 1.Institute of Liver Diseases, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  2. 2.Department of Gastroenterology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China

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