Before this study, scientists had linked use of celecoxib capsules (commonly known as Celebrex) to prevention of cancer, but the way in which the medication acted in cancer cells was unknown.
Now, investigators have found that celecoxib capsules stop a key transcription factor known as Sp1 from turning on multiple genes in cancer cells known to be associated with cancer growth. One of those genes triggers production of vascular endothelial growth factor (VEGF), the predominant angiogenic factor that leads blood vessels to grow to feed tumors.
The findings were published in the Proceedings for the 2003 Annual Meeting of the American Association for Cancer Research.
"Our results provide a novel molecular mechanism for the antitumor activity of celecoxib," says Keping Xie, M.D., Ph.D., assistant professor in the department of gastrointestinal medical oncology.
Xie adds that although the study was conducted in models of pancreatic cancer, the results likely describe how celecoxib interferes with development of a number of common cancers that all involve the Sp1/VEGF pathway.
"Pancreatic cancer overexpresses Sp1, which then drives VEGF overexpression," says Xie. "This same molecular activity is also found in colon, prostate, gastric and breast cancer."
Now that the mechanism by which celecoxib inhibits cancer growth is known, it may be possible to tailor the drug to be even more powerful, Xie says. Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) known as a cox-2 inhibitor, and this new study demonstrates that cox-2 inhibits VEGF through the Sp1 transcription factor.
The researchers used both pancreatic cell cultures and an animal model of the disease to draw their conclu
Contact: Laura Sussman
University of Texas M. D. Anderson Cancer Center