Combination chemotherapy with JTE-522, a novel selective cyclooxygenase-2 inhibitor, and cisplatin against gastric cancer cell lines in vitro and in vivo

COX-2 over-expression occurs in various cancers, but the role of COX-2 in cancer progression remains to be elucidated. We examined the inhibitory effects of a novel selective COX-2 inhibitor, JTE-522 (JT), against gastric cancer cell lines (TMK-1, MKN-45 and MKN-74) alone and in combination with cisplatin (CDDP). The antitumor activity of JTE-522 was evaluated by MTT assay, which revealed that JT alone elicits a dose-dependent antitumor activity in vitro. The JT/CDDP combination elicited a synergistic antitumor effect in MKN-45 cells and an additive effect in the other cell lines. In an in vivo study, 10 mg/kg JT and 12 mg/kg CDDP together elicited a synergistic antitumor activity against MKN-45 cells that were subcutaneously transplanted into nude mice. We conclude that JT is a potent antitumor agent in vitro and in vivo and that, in combination with CDDP, it might be a useful treatment strategy for gastric cancer.