title: Blockade of cholecystokinin-2 receptor and cyclooxygenase-2 synergistically induces cell apoptosis, and inhibits the proliferation of human gastric cancer cells in vitro.
abstract: 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.
authors.affiliation: Department of Geriatrics, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu, PR China. weihaosun@hotmail.com
authors.forename: Wei-Hao
authors.initials: WH
authors.lastname: Sun
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Chen
authors.forename: Han
authors.initials: H
authors.lastname: Su
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Qin-Shi
authors.initials: QS
authors.lastname: Zhao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Shao
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Su-Ming
authors.initials: SM
authors.lastname: Zhou
authors.forename: Guo-Xian
authors.initials: GX
authors.lastname: Ding
authors.forename: Yun-Lin
authors.initials: YL
authors.lastname: Cheng
mesh_terms: 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*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D005755:Gastrins; D043887:Receptor, Cholecystokinin B