Saunders D E, Christensen C, Wappler N L, Cho Y L, Lawrence W D, Malone J M, Malviya V K, Deppe G
Department of OB/GYN, Wayne State University, Detroit, Michigan 48201.
Gynecol Oncol. 1993 Nov;51(2):155-9. doi: 10.1006/gyno.1993.1264.
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.
III/IV期子宫内膜腺癌对细胞毒性药物的反应是部分性的且持续时间短，这些结果表明需要新的药物和治疗策略。本研究旨在确定卡铂和维生素D的活性代谢产物1,25-二羟基维生素D3（骨化三醇）对RL95-2子宫内膜癌细胞生长的影响。卡铂是第二代铂类细胞毒性药物。骨化三醇是一种对多种实体瘤（包括卵巢癌）有活性的生物制剂。卡铂以浓度依赖性方式抑制RL95-2细胞的生长，在200微克/毫升时抑制作用最大（78%）。骨化三醇也以浓度依赖性方式抑制RL95-2细胞的生长。80纳摩尔骨化三醇引起的最大抑制率为29%。在5-20微克/毫升卡铂中加入10-50纳摩尔骨化三醇可增强生长抑制作用。使用等效线图分析评估卡铂和骨化三醇之间的相互作用程度，发现在所有检测的药物浓度和比例下均为相加作用。这些结果表明，卡铂和骨化三醇各自抑制RL95-2子宫内膜癌细胞的生长, 并且这两种药物联合使用可相加抑制RL95-2细胞的生长。这些药物对子宫内膜癌的效用值得进一步研究。
