Prevention of azoxymethane-induced colon cancer by combination of low doses of atorvastatin, aspirin, and celecoxib in F 344 rats

Cancer Research
Bandaru S ReddyChinthalapally V Rao

Abstract

Preclinical and clinical studies have provided evidence that aspirin, celecoxib, (cyclooxygenase-2 inhibitor), and statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) inhibit colon carcinogenesis. Chronic use of high doses of these agents may induce side effects in ostensibly normal individuals. Combining low doses of agents may be an effective way to increase their efficacy and minimize toxicity. We assessed the efficacy of atorvastatin (lipitor), celecoxib, and aspirin, given individually at high dose levels and in combination at lower doses against azoxymethane-induced colon carcinogenesis, in male F 344 rats. One day after the last azoxymethane treatment (15 mg/kg body weight, s.c., once weekly for 2 weeks), groups of male F 344 rats were fed the AIN-76A diet or AIN-76A diet containing 150 ppm atorvastatin, 600 ppm celecoxib, and 400 ppm aspirin, 100 ppm atorvastatin + 300 ppm celecoxib, and 100 ppm atorvastatin + 200 ppm aspirin. Rats were killed 42 weeks later, and colon tumors were processed histopathologically and analyzed for cell proliferation and apoptosis immunohistochemically. Administration of these agents individually and in combination significantly suppressed the incidence and multiplicity of colon ad...Continue Reading

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Citations

Sep 20, 2005·Current Gastroenterology Reports·Bandaru S Reddy, Chinthalapally V Rao
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