Additive inhibition of RL95-2 endometrial carcinoma cell growth by carboplatin and 1,25 dihydroxyvitamin D3.
Responses of stage III/IV endometrial adenocarcinomas to cytotoxic agents have been partial and of short duration, results which indicate a need for new agents and therapeutic strategies. This study was undertaken to determine the effects of carboplatin and the active metabolite of vitamin D, 1,25 dihydroxyvitamin D3 (calcitriol), on the growth of RL95-2 endometrial carcinoma cells. Carboplatin is a second-generation platinum-based cytotoxic agent. Calcitriol is a biologic agent that has activity against multiple solid tumors, including ovarian carcinomas. Carboplatin inhibited the growth of RL95-2 cells in a concentration-dependent manner with maximal inhibition (78%) at 200 micrograms/ml. Calcitriol also inhibited RL95-2 growth in a concentration-dependent manner. Maximal inhibition (29%) was elicited by 80 nM calcitriol. Addition of 10-50 nM calcitriol to 5-20 micrograms/ml carboplatin resulted in improved growth inhibition. The degree of interaction between carboplatin and calcitriol was assessed using isobolographic analysis and was found to be additive at all drug concentrations and ratios examined. These results suggest that carboplatin and calcitriol each inhibit the growth of RL95-2 endometrial carcinoma cells and that the combination of these two agents acts additively to inhibit the growth of RL95-2 cells. These agents merit further investigation for their utility against endometrial carcinomas.
Saunders
D E
DE
Department of OB/GYN, Wayne State University, Detroit, Michigan 48201.
Christensen
C
C
Wappler
N L
NL
Cho
Y L
YL
Lawrence
W D
WD
Malone
J M
JM
Malviya
V K
VK
Deppe
G
G
D000230:Adenocarcinoma / Q000188:drug therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002117:Calcitriol / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000188:drug therapy*
D016190:Carboplatin; D002117:Calcitriol