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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
Author(s) -
Senzaki Michiyo,
Ishida Saori,
Yada Ayumi,
Hanai Masaharu,
Fujiwara Kosaku,
Inoue ShinIchi,
Kimura Tomio,
Kurakata Shinichi
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23250
Subject(s) - cyclooxygenase , celecoxib , pharmacology , cisplatin , ratón , cox 2 inhibitor , medicine , potency , angiogenesis , chemotherapy , adenocarcinoma , enzyme inhibitor , fluorouracil , chemistry , cancer , cancer research , in vitro , enzyme , biochemistry
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.