Reovirus decreases azoxymethane-induced aberrant crypt foci and colon cancer in a rodent model.
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.
Alain
T
T
Department of Medical Sciences, University of Calgary, Calgary, Alberta, Canada.
Wong
J F
JF
Endersby
R
R
Urbanski
S J
SJ
Lee
P W
PW
Muruve
D A
DA
Johnston
R N
RN
Forsyth
P A
PA
Beck
P L
PL
D000230:Adenocarcinoma / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002273:Carcinogens / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D018165:Orthoreovirus / Q000502:physiology*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D001397:Azoxymethane