1. ¹Department of Medical Sciences, University of Calgary, Calgary, Alberta, Canada
2. ²Faculty of Medicine, Division of Gastroenterology, Gastrointestinal Research Group and Mucosal Inflammation Research Group, University of Calgary, Calgary, Alberta, Canada
3. ³Department of Pathology, University of Calgary, Calgary, Alberta, Canada
4. ⁴Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada
5. ⁵Department of Medicine, University of Calgary, Calgary, Alberta, Canada
6. ⁶Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada

Correspondence: Dr PL Beck, Faculty of Medicine, Division of Gastroenterology, Gastrointestinal Research Group and Mucosal Inflammation Research Group, University of Calgary, Health Sciences Center, 3330 Hospital Drive N.W. Calgary, Alberta T2N 4N1, Canada. E-mail: plbeck@ucalgary.ca

Received 16 October 2006; Revised 2 April 2007; Accepted 19 April 2007; Published online 13 July 2007.

Abstract

Reovirus type 3 Dearing has demonstrated oncolytic efficacy in vitro and in vivo against a variety of cancer cell lines, tumor xenografts and syngeneic cancer models. In this study, we investigated the effectiveness of reovirus against aberrant crypt foci (ACF) and colon cancer induced by the carcinogen azoxymethane (AOM) in an immunocompetent rat model. Sprague–Dawley rats received 15 mg/kg AOM intraperitoneally once per week for 4 weeks and reovirus was administered rectally once a week for 5 weeks starting 20 weeks after the last dose of AOM. Two weeks after completion of reovirus therapy, animals were examined for tumor burden in the colon and other tissues. Reovirus-treated animals showed a decrease in total ACF numbers (P=0.014), in large ACFs (P=0.0069) and in tumor number (P=0.03) compared to vehicle-treated animals. Fewer obstructing tumors in the colon (P=0.07) and duodenum (P=0.03) and reduced hepatic metastases were also noted. In addition, a tumor cell line derived from hepatic metastases was found to be susceptible to reovirus in vitro. Our results show that repeated rectal reovirus administration had some efficacy in the treatment and prevention of AOM-induced ACFs, colon cancers and metastases.