Effect of retinoids on xenotransplanted human mammary carcinoma cells in athymic mice.
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 micrograms 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 micrograms 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.
Halter
S A
SA
Department of Pathology, Vanderbilt University, Nashville, Tennessee 37232.
Fraker
L D
LD
Adcock
D
D
Vick
S
S
D000818:Animals; D002277:Carcinoma / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015474:Isotretinoin; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012176:Retinoids / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014212:Tretinoin / Q000627:therapeutic use
D012176:Retinoids; D014212:Tretinoin; D015474:Isotretinoin