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...

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Veröffentlicht in:Cancer letters 2008-05, Vol.263 (2), p.302-311
Hauptverfasser: Sun, Wei-Hao, Zhu, Feng, Chen, Guo-Sheng, Su, Han, Luo, Cheng, Zhao, Qin-Shi, Zhang, Yuan, Shao, Yun, Sun, Jian, Zhou, Su-Ming, Ding, Guo-Xian, Cheng, Yun-Lin
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Sprache:eng
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Zusammenfassung: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.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2008.01.012