CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivo
| Autor: | Yu-Nan Zhang, Yuhu Song, Junwei Yan, Jingjun Yan, Qian Wu, Xing-Xing He |
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| Rok vydání: | 2015 |
| Předmět: |
Transcriptional Activation
0301 basic medicine Carcinoma Hepatocellular Mice Nude Antineoplastic Agents Apoptosis Biology medicine.disease_cause Mice 03 medical and health sciences Transactivation 0302 clinical medicine In vivo Cell Line Tumor In Situ Nick-End Labeling medicine Animals Humans Cell Proliferation Mutation Reverse Transcriptase Polymerase Chain Reaction Cell growth Cell Cycle Liver Neoplasms General Medicine Cell cycle medicine.disease Molecular biology In vitro Pyrimidines 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Female Tumor Suppressor Protein p53 Liver cancer Neoplasm Transplantation |
| Zdroj: | Tumor Biology. 37:807-815 |
| ISSN: | 1423-0380 1010-4283 |
| DOI: | 10.1007/s13277-015-3857-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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