Reference Detail

Ref Type

Journal Article

PMID

(26250460)

Authors

He XX, Zhang YN, Yan JW, Yan JJ, Wu Q, Song YH

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
Tumour biology : the journal of the International Society for Oncodevelopmental	37	1	2016 Jan	807-15	Tumour Biol

URL

Abstract Text

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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
TP53 R249S	hepatocellular carcinoma	sensitive	CP-31398	Preclinical - Cell line xenograft	Actionable	In a preclinical study, treatment with CP-31398 resulted in decreased proliferation, increased apoptosis, and cell-cycle arrest in a hepatocellular carcinoma cell line harboring TP53 R249S in culture, and inhibited tumor growth in xenograft models (PMID: 26250460).	26250460
TP53 Y220C	hepatocellular carcinoma	sensitive	CP-31398	Preclinical - Cell culture	Actionable	In a preclinical study, treatment with CP-31398 resulted in decreased proliferation, increased apoptosis, and cell-cycle arrest in a hepatocellular carcinoma cell line harboring TP53 Y220C in culture (PMID: 26250460).	26250460