Painkillers May Ward Off Ovarian Cancer

Anti-inflammatory drugs could lower tumor risk, researchers say

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By
HealthDay Reporter

MONDAY, March 29, 2004 (HealthDayNews) -- Scientists say they've uncovered a critical clue about why painkillers such as aspirin, ibuprofen, Celebrex, and Vioxx might help prevent ovarian cancer.

These popular anti-inflammatory medications, which inhibit the cox-2 enzyme, appear to slow the rapid turnover of cells within the ovary and reduce the risk for potentially malignant cells, researchers at the Fox Chase Cancer Center in Philadelphia report.

"It's a novel mechanism for how the cox-2 enzyme works," says lead researcher Dr. Xiang-Xi (Mike) Xu. "After we published this, people said, 'Oh, yeah, that looks really obvious.' But previously nobody had stumbled on this before."

Their findings were presented on March 28 at the American Association for Cancer Research's annual meeting in Orlando, Fla.

Ovarian cancer is the fifth leading cancer killer of American women, claiming nearly 15,000 lives per year. The disease, while relatively uncommon, has an especially high fatality rate because ovarian tumors tend to escape detection until the cancer has already spread to other organs.

In its research, Xu's team focused on what the researchers knew to be the prime tumor site within an ovary. "Ninety percent of cancers, including ovarian cancer, come from the layer of cells on the surface of tissue, called epithelial cells," Xu explains.

Epithelial cells are typically organized side by side in a collagen "grid" called the basement membrane. While examining ovarian epithelial cells in the lab, the researchers discovered that overexpression of the cox-2 enzyme can seriously damage the membrane.

According to Xu, destruction of the basement membrane has a negative impact on the life cycle of epithelial cells. "The basement membrane not only organizes them but it gives them signals, too," he explains, keeping normal, healthy cells alive while weeding out mutated cells. Cox-2 destruction of the basement membrane "speeds up the accumulation of mutant or precursor cells, increasing the chances of getting cancer," Xu says.

Cox-2 is best known for its role in triggering inflammatory responses that, if misdirected, can lead to headache or arthritic pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen block both cox-1 and cox-2 enzymes, while the new arthritis medications Celebrex and Vioxx relieve pain by reducing the expression of cox-2 only. (The cox-1 enzyme also protects the stomach lining, and because Celebrex and Vioxx don't inhibit it, they're prescribed to people with gastrointestinal problems.)

The U.S. Food and Drug Administration has approved these drugs for the prevention of colon cancer, and studies have suggested the drugs might help reduce a woman's chances of breast cancer.

Xu now believes cox-2 inhibitors may help prevent ovarian cancer by reducing the enzyme's destruction of the basement membrane.

He also notes that "cox-2, besides inflammation, has other functions in our body, including [stimulation of] ovulation."

"Every time you ovulate, you have to get rid of the basement membrane," Xu says, and "it's known that the more a woman ovulates, the more her chances of getting ovarian cancer." Indeed, women who have fewer ovulations over a lifetime due to pregnancy, breast-feeding, or use of birth control pills appear to be at lowered risk for ovarian cancer.

The bottom line, according to Xu, is any drug that lowers the activity of cox-2 might reduce ovarian cancer risk.

Dr. Debbie Saslow, director for breast and gynecologic cancers at the American Cancer Society, says the findings provide "new information" on the mechanisms behind ovarian tumors, but cautions "this is still in the basic research stage."

In the meantime, Xu's team plans a population-based study looking at tissue changes in the ovaries of women at especially high risk for ovarian cancer due to a family history of the disease. Comparing tissues collected from NSAID users and nonusers, "we will look at the ovary to see if there are any structural changes -- indicators of either disease or some positive effect of the compounds," Xu says.

Saslow says the real "hot topic" in ovarian cancer research these days is the race for an effective early-detection test, with various screening technologies already winding their way through the FDA approvals process. While it's too early to hope that any one test will be prove effective, "there's been a lot of interest there," she says.

More information

For information on ovarian cancer, check out the National Ovarian Cancer Coalition or the National Cancer Institute.

SOURCES: Xiang-Xi (Mike) Xu, Ph.D., medical science division, Fox Chase Cancer Center, Philadelphia; Debbie Saslow, M.D., director, breast and gynecologic cancer, American Cancer Society, Chicago; March 28, 2004, presentation, American Association for Cancer Research annual meeting, Orlando, Fla.

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