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Aug 2, 2007

COX-2 Inhibitors Delay Pancreatic Cancer Precursors in Mice

  • Nimesulide, a COX-2 inhibitor, delays the progression of precancerous pancreatic lesions in mice, according to researchers at David Geffen School of Medicine at UCLA. The researchers say this is the first study to demonstrate the effect of an anti-inflammatory COX-2 inhibitor on the development of pancreatic cancer.

    “With these results, I certainly wouldn’t say everyone should be taking COX-2 inhibitors to protect against cancer,” warns lead author Guido Eibl, M.D., scientific director of the Hirshberg Laboratory of Pancreatic Cancer Research and adjunct assistant professor at UCLA. “However, with additional studies, we may find COX-2 inhibitors could help prevent pancreatic cancer in high-risk populations.”

    COX-2 is already believed to play some role in tumor growth in breast, colon, and pancreatic cancers. To study the effects of COX-2 on pancreatic intraepithelial neoplasias (PanINs) progression, Dr. Eibl and colleagues focused on the KrasG12D mouse. In this model, low-grade PanINs (stage I or II) begin to appear in the pancreas at one month and high-grade PanINs (stage III) can be found at the six-month stage. Most researchers agree that stage III PanINs are a direct precursor to pancreatic cancer in humans as well as in mice, according to Dr. Eibl. Between 12 and 15 months, Dr. Eibl says the majority of KrasG12D mice will develop pancreatic tumors.

    In the UCLA study one set of mice received a Nimesulide-enriched diet for 10 months and were compared to a control group fed a regular diet. Their analyses revealed that 10% of pancreatic ducts had PanIN-2 or -3 in the mice in the Nimesulide group versus 40% in the control arm.

    Because the pancreases of mice were analyzed at 10 months, before the typical appearance of pancreatic tumors, the team intends to conduct further studies to conclude whether or not Nimesulide can delay the onset of or prevent pancreatic cancer.

    The study was published in the August 1 issue of Cancer Research.



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