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5-Aminosalicylic Acid Given in the Remission Stage of Colitis Suppresses Colitis-Associated Cancer in a Mouse Colitis Model

Authors' Affiliations: ¹ Gastroenterology Division, ² Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan, ³ Department of Pharmacology, Graduate School of Dentistry, Osaka University, Osaka, Japan, and ⁴ Biochemistry Division, National Cancer Center Research Institute, Tokyo, Japan

Requests for reprints: Atsushi Nakajima, Gastroenterology Division, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan. Phone: 81-45787-2640; Fax: 81-45787-8988; E-mail: nakajima-tky{at}umin.ac.jp.

Purpose: The risk of colorectal cancer is increased in patients with inflammatory bowel diseases, especially those with ulcerative colitis (UC). Although 5-aminosalicylic acid (5-ASA) is widely used in the treatment of UC to suppress the colitic inflammation, no studies have been conducted to examine the chemopreventive effect of 5-ASA, given in the remission phase of colitis, against colitis-associated cancer using animal models. We therefore investigated the possible inhibition by peroxisome proliferator-activated receptor- (PPAR) ligands and 5-ASA of colitis-associated colon carcinogenesis in a mouse model.

Experimental Design: A dextran sodium sulfate/azoxymethane–induced mouse colon cancer model was used, and the chemopreventive effects of 5-ASA and PPAR ligands, given in the remission phase of colitis, against colitis-related colon carcinogenesis, were evaluated.

Results: The number of neoplasms in the mice treated with 5-ASA was significantly lower than that in the control mice. In addition, the size of the neoplasms in treated mice was also significantly smaller than that in the control mice. In contrast, no significant suppression in the number or size of the tumors was observed in the mice treated with PPAR ligands. The proliferating cell nuclear antigen–labeling index in the tumor cells of the 5-ASA–treated mice was significantly smaller than that in the control, indicating that 5-ASA reduced tumor cell proliferation.

Conclusion: Our results revealed that 5-ASA given in the remission phase of colitis significantly suppressed the development of colitis-associated cancer in a mouse model, which indicates the clinical importance of adopting chemopreventive strategies even in UC patients in remission.

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