Sulindac inhibits the rate of growth and appearance of colon tumors in the rat
S. A. Skinner, A. G. Penney and P. E. O'Brien
Department of Surgery, Monash University, Alfred Hospital, Prahran, Victoria, Australia.
Sulindac (cis-5-fluoro-2-methyl-1-[p-(methylsulfinyl) benzylidene]
indene-3-acetic acid), an inhibitor of prostaglandin synthesis, has been
reported to cause regression of colon polyps in patients with familial
polyposis coli and Gardner's syndrome. We examined the effect of sulindac
on the growth of primary colon carcinomas in rats. Colon tumors were
induced in 18 rats by repeated subcutaneous administration of
dimethylhydrazine. The site and diameter of each tumor were measured via
laparotomy and colonoscopy. Rats were randomized to receive either sulindac
(10 mg/kg) twice daily or vehicle (0.5% methylcellulose). After 4 weeks of
treatment, the site and size of tumors in the colon were again recorded. In
eight rats receiving sulindac, no new tumors were identified, while in 10
control rats, 13 additional tumors were found after treatment. There was a
significantly greater increase in size of the tumors in the control group
(56.4 mm for 26 tumors) compared with the rats receiving sulindac (9.3 mm
for 14 tumors). We report that sulindac inhibits the rate of development
and the rate of growth of colon tumors in the rat.
Sulindac Sulfide Inhibits Epidermal Growth Factor-induced Phosphorylation of Extracellular-regulated Kinase 1/2 and Bad in Human Colon Cancer Cells
Rice et al.
Cancer Res. 2003;63:616-620.
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Epidemiology of colorectal cancer
Boyle and Leon
Br Med Bull 2002;64:1-25.
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Nonsteroidal Anti-inflammatory Drugs as Anticancer Agents: Mechanistic, Pharmacologic, and Clinical Issues
Thun et al.
JNCI J Natl Cancer Inst 2002;94:252-266.
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Non-steroidal anti-inflammatory drugs with activity against either cyclooxygenase 1 or cyclooxygenase 2 inhibit colorectal cancer in a DMH rodent model by inducing apoptosis and inhibiting cell proliferation
Brown et al.
Gut 2001;48:660-666.
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Inhibition of Extracellular Signal-regulated Kinase 1/2 Phosphorylation and Induction of Apoptosis by Sulindac Metabolites
Rice et al.
Cancer Res. 2001;61:1541-1547.
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Effects of Piroxicam on Prostaglandin E2 Levels in Rectal Mucosa of Adenomatous Polyp Patients: A Randomized Phase IIb Trial
Calaluce et al.
Cancer Epidemiol. Biomarkers Prev. 2000;9:1287-1292.
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Inhibition of rat colon tumors by sulindac and sulindac sulfone is independent of K-ras (codon 12) mutation
de Jong et al.
Am. J. Physiol. Gastrointest. Liver Physiol. 2000;278:G266-G272.
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