Retinoic Acid May Enhance Chemo In Ovarian Ca Cells

SAN FRANCISCO--Retinoic acid appeared to enhance the efficacyof cisplatin (Platinol) and paclitaxel (Taxol) in two of threeovarian cancer cell lines tested, James R. Bosscher, MD, saidin his poster presentation at the Society of Gynecologic Oncologistsmeeting.

Because cisplatin and paclitaxel are the most effective agentsagainst epithelial ovarian cancer, any agent that improves theirefficacy deserves further investigation, Dr. Bosscher told OncologyNews International. He pointed out that retinoic acid, a derivativeof vitamin A, has been shown to be an important influence in celldifferentiation, as well as an effective treatment for other typesof early cancers.

Dr. Bosscher and his colleagues at the University of LouisvilleSchool of Medicine looked at the effects of retinoic acid on threecell lines, two standard epithelial ovarian cancer cell lines(SKOV-3 and OVCAR-3) and UL-1, which was developed at Louisvillefrom the ascites of an ovarian cancer patient.

When the cancer cell lines were exposed to retinoic acid alone,the compound interfered with the doubling rate of the OVCAR-3cell line. Retinoic acid by itself produced no significant effectson the other two cell lines, Dr. Bosscher reported.

When paclitaxel and cisplatin were added to OVCAR-3 and UL-1 celllines that had previously been treated with retinoic acid, thecell kill rate of the two chemotherapies improved. The amountof either cisplatin or paclitaxel required to kill 50% of thecancerous cells was significantly reduced.

Dr. Bosscher noted that the effect of retinoic acid seems to berelated to the presence or absence of cell membrane receptorsfor the compound. In the SKOV-3 ovarian cancer cell line, whichhas fewer retinoic acid receptors, retinoic acid appeared to protectcancer cells from the effects of chemotherapy. The amount of drugrequired to kill 50% of the cancer cells increased when retinoicacid was added--significantly in the case of cisplatin and slightlyfor paclitaxel.

"The next step is to move beyond in vitro cell culture studiesto determine the effect of this treatment in mice, with an eyetoward taking the trials to phase I studies a few years down theroad," Dr. Bosscher said.