Blockade of cholecystokinin-2 receptor and cyclooxygenase-2 synergistically induces cell apoptosis, and inhibits the proliferation of human gastric cancer cells in vitro.
Gastrin and cyclooxygenase-2 (COX-2) play important roles in the carcinogenesis and progression of gastric cancer. However, it remains unknown whether the combination of cholecystokinin-2 (CCK-2) receptor antagonist plus COX-2 inhibitor exerts synergistic anti-tumor effects on human gastric cancer. Here, we demonstrated that the combination of AG-041R (a CCK-2 receptor antagonist) plus NS-398 (a selective COX-2 inhibitor) treatment had synergistic effects on proliferation inhibition, apoptosis induction, down-regulation of Bcl-2 and up-regulation of Bax expression in MKN-45 cells. These results indicate that simultaneous targeting of CCK-2 receptor and COX-2 may inhibit gastric cancer development more effectively than targeting either molecule alone.
Sun
Wei-Hao
WH
Department of Geriatrics, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu, PR China. weihaosun@hotmail.com
Zhu
Feng
F
Chen
Guo-Sheng
GS
Su
Han
H
Luo
Cheng
C
Zhao
Qin-Shi
QS
Zhang
Yuan
Y
Shao
Yun
Y
Sun
Jian
J
Zhou
Su-Ming
SM
Ding
Guo-Xian
GX
Cheng
Yun-Lin
YL
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D005755:Gastrins / Q000032:analysis; D006801:Humans; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors*; D013274:Stomach Neoplasms / Q000473:pathology*
D052246:Cyclooxygenase 2 Inhibitors; D005755:Gastrins; D043887:Receptor, Cholecystokinin B