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

Abstract 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.