BPB Reports

Paper Details

BPB Reports
Vol. 2 No. 6 p.130-133 2019
Sensitization of Gastric Cancer Cells to Irinotecan by p53 Activation
  • Hyeon-Cheol Lee-Okada (Department of Biochemistry, Juntendo University Graduate School of Medicine / h-lee@juntendo.ac.jp)
Shun Zhang 1) 2) , Yoshinori Kohira 1) , Hajime Orita 1) , Momoko Ishimine 3) , Toshiyuki Kobayashi 4) , Sharlyn Mae Buendia Chua 5) , Hirofumi Nakaoka 5) , Ituro Inoue 5) , Okio Hino 4) , Takehiko Yokomizo 3) , Tetsu Fukunaga 1) , Hyeon-Cheol Lee-Okada 3)
1) Department of Gastroenterology and Minimally Invasive Surgery, Juntendo University Hospital , 2) Department of Gastroenterology Surgery, Shanghai East Hospital (East Hospital Affiliated to Tongji University), China , 3) Department of Biochemistry, Juntendo University Graduate School of Medicine , 4) Department of Molecular Pathogenesis, Juntendo University Graduate School of Medicine , 5) Human Genetics Laboratory, National Institute of Genetics
Received: December 11, 2019;   Accepted: December 17, 2019;   Released: December 27, 2019
Keywords: CES2, gastric cancer, irinotecan, p53, nutlin-3a

Irinotecan (camptothecin-11 [CPT-11]) is a topoisomerase I inhibitor that has been used in the treatment of a wide spectrum of cancers including gastric cancer. Recent reports suggest that the expression of CES2, a serine hydrolase that converts irinotecan to its active compound SN-38, is regulated by the tumor-suppressor p53. In this study, we investigated whether irinotecan acted synergistically with a p53 activator nutlin-3a in human gastric cancer cells. Nutlin-3a treatment enhanced the expression of CES2 in gastric cancer cell lines with wild-type p53. However, this effect was not observed in cells with non-functional p53. Irinotecan showed synergistic antitumor effects in combination with nutlin-3a in gastric cancer cells with wild-type p53, whereas the survival of cells with non-functional p53 was not significantly affected by the presence of nutlin-3a. These results provide evidence that p53 activation can enhance the antitumor effect of irinotecan or other anticancer prodrugs activated by CES2 in gastric cancer cells through upregulation of CES2 expression.