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 |
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Format: | Artikel |
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. |
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ISSN: | 0304-3835 1872-7980 |
DOI: | 10.1016/j.canlet.2008.01.012 |