CS‐706, a novel cyclooxygenase‐2 selective inhibitor, prolonged the survival of tumor‐bearing mice when treated alone or in combination with anti‐tumor chemotherapeutic agents

The potent chemopreventive activity of cyclooxygenase‐2 (COX‐2) inhibitors has been demonstrated in a number of preclinical studies, but their potency in antitumor activity is still in dispute. In this report, we demonstrate the potent antitumor activity of a novel COX‐2 inhibitor, CS‐706 in mouse colorectal adenocarcinoma colon 26 tumor‐bearing mice treated with or without antitumor chemotherapeutic agents. Daily oral administration of CS‐706 at doses of 3–100 mg/kg from the day of tumor inoculation (Day 0) inhibited tumor growth dose‐dependently, and the maximal inhibition was 67% at a dose of 100 mg/kg. In contrast, celecoxib, a well‐known COX‐2 inhibitor, did not inhibit tumor growth at doses up to 100 mg/kg. Furthermore, CS‐706 at a dose of 1 mg/kg or above markedly prolonged the survival time of tumor‐bearing mice. Administration of 30 mg/kg CS‐706 from Day 7 combined with a single intravenous treatment of 10 mg/kg cisplatin on Day 7 completely regressed the tumors in all tumor‐bearing mice examined, whereas only in 1 of 10 mice tumor was regressed with cisplatin treatment. Similar combination effects were observed with 10 mg/kg CS‐706 and 60 mg/kg 5‐fluorouracil (5‐FU). Moreover, 10 mg/kg CS‐706 significantly inhibited angiogenesis induced by implanted chambers with colon 26 cells in a dorsal air sac assay in mice. Collectively, these results suggest that CS‐706 is a potent antitumor agent, especially in combination with conventional chemotherapeutic agents, and that the anti‐angiogenic activity of CS‐706 may contribute at least in part to its marked antitumor activity. © 2007 Wiley‐Liss, Inc.