Blocking COX-1 slows mice tumour growth
enzyme, might lead the way to prevent and treat the most common and
fatal form of ovarian cancer.
The finding, that COX-1 inhibition slowed the growth of epithelial ovarian tumours in a mouse model of the disease, is surprising, said Sudhansu Dey, senior author of the paper.
The COX enzyme class has not had the most favourable coverage recently, with the FDA questioning the safety of COX-2 arthritis drugs, such as Celebrex, Vioxx and Bextra. Whilst previous studies have linked high levels of the COX-2 enzyme to colorectal and other cancers, this latest news clearly shows the class of enzyme is not entirely accountable and may even provide a target for which an effective therapy can be based upon.
Several previous studies have reported high COX-2 levels in ovarian tumours. Most of these, however, used antibodies to detect COX-2 expression. "We now know that many of the commercially available antibodies cross react with both COX-1 and COX-2," said Sudhansu Dey, senior author of the paper
"These results establish the foundation for further studies and clinical trials using the novel approach of targeting COX-1 for the prevention and treatment of ovarian cancer," Dey said.
In the current study, the researchers, from the Vanderbilt University Medical Centre used Orsulic's model to test whether celecoxib (Celebrex), a selective COX-2 inhibitor, and SC-560, an experimental drug that selectively blocks COX-1, slowed tumour growth when these cells were transplanted into mice.
They found that while Celebrex had little effect, the COX-1 blocker dramatically reduced tumour growth. The drug also blocked production by COX-1 of prostacyclin, a member of a family of potent, hormone-like substances called prostaglandins that play a role in a wide variety of physiological functions including pain, inflammation and, presumably, cancer.
Whereas prostacyclin is the predominant prostaglandin found in mouse ovarian tumors, another prostaglandin, PGE2, seems to be generated in higher quantities in human ovarian cancers. This suggests that it's not the particular enzyme - COX-1 or COX-2 - but downstream factors, including prostaglandins that initiate tumour growth, Dey said.
He added that further studies were to be conducted to determine whether aspirin and other non-steroidal anti-inflammatory drugs, which block both COX enzymes, might improve treatment of epithelial ovarian cancer.
According to the American Cancer Society, more than 22,000 women in the United States will be diagnosed with ovarian cancer this year, and more than 16,000 will die from the disease. Ovarian cancer is the fourth leading cause of cancer death in American women after lung, breast and colorectal cancer.
Eighty-five per cent of human ovarian tumours arise from the epithelium or surface layer of tissue that surrounds the ovaries. While the incidence of ovarian cancer has declined recently, the death rate has not, in part because it is difficult to diagnose the disease in the early stages.
The study is published on the web site of the journal Cancer Research.
