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Effect of Retinoids on Xenotransplanted Human Mammary Carcinoma Cells in Athymic Mice¹

Department of Pathology, Vanderbilt University, and the Veterans Administration Medical Center, Nashville, Tennessee 37232

Previous studies have shown dose-dependent growth inhibition of the human mammary carcinoma cell line MDA-MB-231 xenotransplanted in athymic mice using retinol. In this study, the growth inhibitory effect of retinoic acid (RA) and 13-cis-retinoic acid (13-cis-RA) was examined in vitro and in vivo. With both agents there was dose-related growth inhibition in monolayer culture. The MDA-MB-231 cell line was more sensitive in monolayer culture to 13-cis-RA than to RA. Anchorage-independent growth of the MDA-MB-231 cell line was also inhibited by both of these agents but only in a dose-dependent manner with 13-cis-RA. Athymic mice inoculated with MDA-MB-231 human mammary carcinoma cells were treated with various doses of RA and 13-cis-RA for 30 days. RA doses greater than 90 µg were clinically toxic to the animals. There was a decrease in tumor size with all doses of RA tested but not in a dose-related fashion. Response at the higher doses of RA may be related to subclinical toxicity. Doses of 13-cis-RA above 300 µg were clinically toxic. Unlike RA, there was no statistically significant decrease in tumor size with treatment with 13-cis-RA. These findings show that there is significant reduction in growth in vivo of the human mammary carcinoma cell line MDA-MB-231 after treatment with RA. However, in vivo response to the retinoids is not always predicted by in vitro methods.

¹ This investigation was supported in part by the Medical Research Service of the Veterans Administration, USPHS Grant CA-19429, and by a Biomedical Research Support Grant from NIH. Research procedures were in accordance with the ethical standards of the Vanderbilt and Nashville Veterans Administration Medical Center Animal Care Committees. This work was presented in part at the annual meeting of the American Association for Cancer Research, Atlanta, GA, 1987.

² To whom reprint requests should be addressed, at Department of Pathology, Vanderbilt University School of Medicine, Medical Center North, Nashville, TN 37232

Received 10/ 5/87. Revised 2/22/88. Accepted 4/ 1/88.

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