NO-donating aspirin inhibits intestinal carcinogenesis in Min (APC ^Min/+) mice

The chemopreventive effect of nitric oxide-releasing aspirin (NO-ASA) against gastrointestinal tumorigenesis was evaluated in Min (APC ^Min/+) mice. NO-ASA consists of a traditional ASA that bears covalently attached to it an NO-releasing moiety. Four groups (N=10) of six-week-old female C57BL/6J APC^Min/+ and the corresponding C57BL/6J^+/+ wild type mice were treated either with vehicle or NO-ASA 100mg/kg/day intrarectally for 21 days. There were no signs of overt toxicity including gastrointestinal toxicity from NO-ASA. Vehicle treated Min mice had 24.7±3.8 tumors (mean± SEM) and NO-ASA treated Min mice had 10.1±1.4 tumors (59% reduction; P<0.001). Wild type mice showed no tumors. NO-ASA did not affect cell proliferation in small intestinal mucosa, determined by immunohistochemical staining for PCNA. Our findings establish the strong inhibitory effect of NO-ASA in intestinal carcinogenesis in the Min mouse and suggest that this agent merits further evaluation as a chemopreventive agent against colon cancer.