Inhibition of COX-2 Slows Development of Pancreatic Cancer in Mouse Model

Cancer researchers working with a mouse model of human pancreatic cancer have found that nimesulide, a cyclooxygenase-2 (COX-2) inhibitor, delayed the progression of precancerous pancreatic lesions.

Investigators at the University of California, Los Angeles (USA) studied the development of pancreatic intraepithelial neoplasias (PanINs) in the KrasG12D mouse, an animal model that mimics the early stages of pancreatic cancer. In the KrasG12D mouse, low-grade PanINs (stage I or II) begin to appear in the pancreas of the mice at age one month, and by 12 to 15 months, the majority of the animals will have developed pancreatic tumors.

In the current study, a population of KrasG12D mice were divided into two groups. One group was fed a diet supplemented with the selective COX-2 inhibitor nimesulide (400 ppm) while the other group received a control diet of regular mouse chow. After 10 months the animals were sacrificed and the status of their pancreatic lesions evaluated.

Results published in the August 1, 2007, issue of the journal Cancer Research revealed that animals fed the COX-2 inhibitor had significantly fewer PanIN-2 and PanIN-3 lesions than those in the control group. Approximately 10% of all pancreatic ducts in the nimesulide-fed animals showed PanIN-2 or PanIN-3 lesions, whereas more than 40% of the pancreatic ducts in the control animals had PanIN-2 or PanIN-3 lesions. Reduced pancreatic prostaglandin E2 levels n the nimesulide-fed animals showed that the drug had been effective in inhibiting COX-2 activity.

"By inhibiting COX-2 in human patients, we may have an option to delay the progression of lesions,” said senior author Dr. Guido Eibl, professor of surgery and pancreatic cancer research at the University of California, Los Angeles. "Pancreatic cancer is so deadly because it often goes undetected until it is too late. If a patient is at a high-risk for developing pancreatic cancer, a COX-2 inhibitor may offer some protection.”


Related Links:
University of California, Los Angeles