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

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• 作者：Xingxing He (1)
  Xinjuan Kong (2)
  Junwei Yan (1)
  Jingjun Yan (1)
  Yunan Zhang (1)
  Qian Wu (1)
  Ying Chang (1)
  Haitao Shang (3)
  Qian Dou (2)
  Yuhu Song (3)
  Fang Liu (4)
  
  1. Institute of Liver Diseases ; Tongji Hospital ; Tongji Medical College ; Huazhong University of Science and Technology ; Wuhan ; People鈥檚 Republic of China
  2. Department of Gastroenterology ; The Affiliated Hospital of Medical College of Qingdao University ; Qingdao ; People鈥檚 Republic of China
  3. Department of Gastroenterology ; Union Hospital ; Tongji Medical College ; Huazhong University of Science and Technology ; Wuhan ; 430022 ; People鈥檚 Republic of China
  4. Institute of Hematology ; Union Hospital ; Tongji Medical College ; Huazhong University of Science and Technology ; Wuhan ; 430022 ; People鈥檚 Republic of China
  
• 关键词：Mutant p53 ; Colorectal cancer ; CP ; 31398 ; Apoptosis ; Cell cycle
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：36
• 期：3
• 页码：1437-1444
• 全文大小：1,496 KB
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• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

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.