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NSAID drug protects against intestinal tumors in mice, despite poor diet and gene losses

In mouse models of intestinal cancer, use of an anti-inflammatory drug eliminated all of the cancer-causing risks produced by a high-fat Western-style diet - even when several genetic brakes to cancer formation were missing in the animals, say researchers from the Albert Einstein Cancer Center.

The investigators, who presented their findings at the 96th Annual Meeting of the American Association for Cancer Research, say that while the results do not yet have relevance for preventing human colon cancer, they do illustrate the interplay between genes and common nutritional and medicinal agents in development of cancer in the intestines.

The drug they tested, sulindac, was a highly effective chemoprevention agent, the researchers say, because it worked to induce expression of the p21 gene, which they found put a firm stop on tumor formation even though the mice were missing two key tumor suppressor genes (p27 and APC) and were fed a diet high in fat and low in calcium and vitamin D.

"It appears that p21 activation through sulindac offers protection against both a lack of tumor suppressor genes as well as poor diet," says the lead author, WanCai Yang, M.D., an assistant professor of medicine. While the drug is a NSAID (non-steroidal anti-inflammatory drug) and a COX-2 inhibitor, Yang believes its chemoprotective effects come via novel pathways that affect p21 expression.

The study builds upon a body of research conducted by Yang and Leonard Augenlicht, Ph.D., at the Albert Einstein Cancer Center that has used knockout mouse models to explore the role of genes and diet, including the finding that inactivation of the p21 gene accelerated tumor formation and that loss of this gene eliminated the ability of sulindac to inhibit tumor formation. Their earlier studies also showed that mice that lacked p27, another tumor suppressor gene, had a higher risk of developing tumors in both the small and large intestine.

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Source:American Association for Cancer Research


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