5-aminosalicylic acid given in the remission stage of colitis suppresses colitis-associated cancer in a mouse colitis model.
OBJECTIVE
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-gamma (PPARgamma) ligands and 5-ASA of colitis-associated colon carcinogenesis in a mouse model.


METHODS
A dextran sodium sulfate/azoxymethane-induced mouse colon cancer model was used, and the chemopreventive effects of 5-ASA and PPARgamma 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 PPARgamma 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.


CONCLUSIONS
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.
Ikeda
Ikuko
I
Gastroenterology Division, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Tomimoto
Ayako
A
Wada
Koichiro
K
Fujisawa
Toshio
T
Fujita
Koji
K
Yonemitsu
Kyoko
K
Nozaki
Yuichi
Y
Endo
Hiroki
H
Takahashi
Hirokazu
H
Yoneda
Masato
M
Inamori
Masahiko
M
Kubota
Kensuke
K
Saito
Satoru
S
Nagashima
Yoji
Y
Nakagama
Hitoshi
H
Nakajima
Atsushi
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001835:Body Weight; D003092:Colitis / Q000150:complications* / Q000188:drug therapy*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008024:Ligands; D008297:Male; D019804:Mesalamine / Q000494:pharmacology*; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy*; D047495:PPAR gamma / Q000378:metabolism; D012074:Remission Induction; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008024:Ligands; D047495:PPAR gamma; D019804:Mesalamine