NDLI: CP-31398 prevents the growth of p53-mutated colorectal cancer cells in vitro and in vivo.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	He, Xingxing Kong, Xinjuan Yan, Junwei Yan, Jingjun Zhang, Yunan Wu, Qian Chang, Ying Shang, Haitao Dou, Qian Song, Yuhu Liu, Fang
Description	Author Affiliation: He X ( Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.)
Abstract	Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Small molecule CP-31398 was shown to restore mutant p53 tumor suppressor functions in cancer cells. Here, we determined the effects of CP-31398 on the growth of p53-mutated colorectal cancer (CRC) cells in vitro and in vivo. CRC cells which carry p53 mutation in codon 273 were treated with CP-31398 and the control, and the effects of CP-31398 on cell cycle, cell apoptosis, and proliferation were determined. The expression of p53-responsive downstream genes was evaluated by quantitative reverse transcriptase PCR (RT-PCR) and Western blot. CP-31398 was administrated into xenograft tumors created by the inoculation of HT-29 cells, and then the effect of CP-31398 on the growth of xenograft tumors was examined. CP-31398 induced p53 downstream target molecules in cultured HT-29 cells, which resulted in the inhibition of CRC cell growth assessed by the determination of cell cycle, apoptosis, and cell proliferation. In xenograft tumors, CP-31398 modulated the expression of Bax, Bcl-2, caspase 3, cyclin D, and Mdm2 and then blocked the growth of xenograft tumors. CP-31398 would be developed as a therapeutic candidate for p53-mutated CRC due to the restoration of mutant p53 tumor suppressor functions.
File Format	HTM / HTML
ISSN	10104283
Issue Number	3
Volume Number	36
e-ISSN	14230380
Journal	Tumor Biology
Language	English
Publisher	Springer
Publisher Date	2015-03-01
Publisher Place	Netherlands
Access Restriction	Subscribed
Subject Keyword	Discipline Medicine__semicolon__oncology Colorectal Neoplasms Drug Therapy Pyrimidines Pharmacology Tumor Suppressor Protein P53 Genetics Animals Apoptosis Drug Effects Caspase 3 Cell Cycle Cell Line, Tumor Cell Proliferation Pathology Cyclin D Ht29 Cells Humans Mice Mice, Inbred Balb C Mice, Nude Proto-oncogene Proteins C-bcl-2 Proto-oncogene Proteins C-mdm2 Xenograft Model Antitumor Assays Methods Bcl-2-associated X Protein Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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