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.
基金：
National Natural Science Foundation of China [81072003, 81270506, 81101824, 81302112]; Outstanding Youth Science Foundation of Tongji Hospital [YXQN005]; Youth Sciences and Technology Chenguang Planning of Wuhan [2014070404010219]; Fundamental Research Funds for the Central Universities [2014QN084]
第一作者单位：[1]Huazhong Univ Sci & Technol,Inst Liver Dis,Tongji Hosp,Tongji Med Coll,Wuhan 430022,Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
He Xingxing,Kong Xinjuan,Yan Junwei,et al.CP-31398 prevents the growth of p53-mutated colorectal cancer cells in vitro and in vivo[J].TUMOR BIOLOGY.2015,36(3):1437-1444.doi:10.1007/s13277-014-2389-8.
APA：
He, Xingxing,Kong, Xinjuan,Yan, Junwei,Yan, Jingjun,Zhang, Yunan...&Liu, Fang.(2015).CP-31398 prevents the growth of p53-mutated colorectal cancer cells in vitro and in vivo.TUMOR BIOLOGY,36,(3)
MLA：
He, Xingxing,et al."CP-31398 prevents the growth of p53-mutated colorectal cancer cells in vitro and in vivo".TUMOR BIOLOGY 36..3(2015):1437-1444
