Celecoxib, a COX2 Inhibitor, Prevents Colon Cancer in Animals

NEW ORLEANS--In a mouse model of colon cancer, the anti-inflammatory drug celecoxib prevented formation of tumors and caused regression of existing tumors, according to research presented at the 89th annual meeting of the American Association for Cancer Research (AACR).

The new drug celecoxib is currently in phase III clinical trials as a treatment for osteoarthritis, rheumatoid arthritis, and pain. It acts by inhibiting the cyclo-oxygenase 2 (COX2) enzyme, which is released during inflammation. Concentrations of this enzyme also rise in colon polyps and cancers. Previous studies suggested that aspirin and sulindac, anti-inflammatory drugs that inhibit COX1 and COX2, can also prevent colon cancer.

In this study, Russell F. Jacoby, MD, associate professor of medicine and director of the Colon Cancer Prevention Program at the University of Wisconsin Comprehensive Cancer Center, Madison; Ronald A. Lubet, PhD, program director of the NCI’s Chemoprevention Branch; and their colleagues tested the ability of celecoxib to prevent colon cancer.

They used 96 Min C57BL-6J mice, a strain that develops dozens of tumors in the small intestines as well as tumors in the colon. The mice received doses of 0, 150, 500, or 1,500 parts per million of celecoxib in their diet. Some started the treatment at age 30 days (when weaned), while others did not start until age 55 days. At age 80 days, all were examined for intestinal tumors.

All the control mice had tumors, an average of 22 to 23 per mouse. But in the mice treated with celecoxib, both the percentage of mice with tumors and the average number of tumors dropped as the dose increased.

The mice that started treatment earlier had fewer tumors. For example, only 29% of the mice started on 1,500 parts per million at 30 days of age developed tumors, and they averaged only 6.5 tumors each. Of mice that started on that dose at age 55 days, 48% developed tumors, with an average of 11.1 each.

In contrast to previous tests of the antitumor effects of anti-inflammatory drugs, in this experiment, the mice did not lose weight or develop ulcers.

These results show that celecoxib was able both to prevent tumors from forming in mice when used from a young age and to cause already formed tumors to regress when started later.

The genetic mutation that causes polyp formation in Min mice is the same one that causes polyp formation in humans with familial adenomatous polyp-osis (FAP), an inherited condition in which patients develop hundreds of colon polyps. Thus, these results suggest that COX2 inhibitors should be tested for their ability to prevent colon polyps and colon cancer in people with FAP and possibly also other people at risk for colon cancer.