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Retinoic Acid May Enhance Chemo In Ovarian Ca Cells

Retinoic Acid May Enhance Chemo In Ovarian Ca Cells

SAN FRANCISCO--Retinoic acid appeared to enhance the efficacy of cisplatin (Platinol) and paclitaxel (Taxol) in two of three ovarian cancer cell lines tested, James R. Bosscher, MD, said in his poster presentation at the Society of Gynecologic Oncologists meeting.

Because cisplatin and paclitaxel are the most effective agents against epithelial ovarian cancer, any agent that improves their efficacy deserves further investigation, Dr. Bosscher told Oncology News International. He pointed out that retinoic acid, a derivative of vitamin A, has been shown to be an important influence in cell differentiation, as well as an effective treatment for other types of early cancers.

Dr. Bosscher and his colleagues at the University of Louisville School of Medicine looked at the effects of retinoic acid on three cell lines, two standard epithelial ovarian cancer cell lines (SKOV-3 and OVCAR-3) and UL-1, which was developed at Louisville from 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-3 cell line. Retinoic acid by itself produced no significant effects on the other two cell lines, Dr. Bosscher reported.

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

Dr. Bosscher noted that the effect of retinoic acid seems to be related to the presence or absence of cell membrane receptors for the compound. In the SKOV-3 ovarian cancer cell line, which has fewer retinoic acid receptors, retinoic acid appeared to protect cancer cells from the effects of chemotherapy. The amount of drug required to kill 50% of the cancer cells increased when retinoic acid was added--significantly in the case of cisplatin and slightly for paclitaxel.

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

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