Cho Y L, Christensen C, Saunders D E, Lawrence W D, Deppe G, Malviya V K, Malone J M
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Cancer Res. 1991 Jun 1;51(11):2848-53.
The effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and platinum treatments (both singly and combined) on the growth inhibition of MCF-7 cells, an epithelial cell line shown to possess specific receptors for 1,25(OH)2D3, were evaluated. The inhibitory effects of 1,25(OH)2D3 and platinum on MCF-7 cell proliferation in vitro were time and dose related. The data showed that 10 nM and 100 nM 1,25(OH)2D3 inhibited MCF-7 cell growth by 10.8 +/- 2.4% and 34.9 +/- 0.5% (mean +/- SE), respectively. The degrees of growth inhibition induced by 0.2 to 200 micrograms/ml of cis-diammine-1,1-cyclobutane dicarboxylatoplatinum(II) (carboplatin) were slightly less than those induced by 0.02 to 20 micrograms/ml of cis-diamminedichloroplatinum(II) (cisplatin). The combined administration of 10 nM and 100 nM 1,25(OH)2D3 with either carboplatin (200 to 0.2 micrograms/ml) or cisplatin (20 to 0.02 micrograms/ml) was evaluated. Addition of 1,25(OH)2D3 to the platinum resulted in marginal to marked enhancement of growth inhibition over that observed with either platinum alone. The strength of these interactions varied inversely with the dose of the platinum drugs. Evaluation of drug interactions with isobolograms showed that at near-serum levels, carboplatin or cisplatin interacted synergistically with 1,25(OH)2D3 to inhibit MCF-7 cell growth. Our findings suggest potential usefulness in combining 1,25(OH)2D3, a biological modifier, with cytotoxic agents for the treatment of malignant disease.
评估了1,25 - 二羟基维生素D3 [1,25(OH)2D3] 与铂类治疗（单独及联合使用）对MCF - 7细胞生长抑制的影响，MCF - 7细胞系是一种已证实具有1,25(OH)2D3特异性受体的上皮细胞系。1,25(OH)2D3和铂对体外MCF - 7细胞增殖的抑制作用具有时间和剂量依赖性。数据显示，10 nM和100 nM的1,25(OH)2D3分别使MCF - 7细胞生长抑制10.8±2.4%和34.9±0.5%（平均值±标准误）。0.2至200微克/毫升的顺 - 二氨 - 1,1 - 环丁烷二羧酸铂(II)（卡铂）诱导的生长抑制程度略低于0.02至20微克/毫升的顺 - 二氨二氯铂(II)（顺铂）。评估了10 nM和100 nM的1,25(OH)2D3与卡铂（200至0.2微克/毫升）或顺铂（20至0.02微克/毫升）的联合给药情况。在铂类药物中添加1,25(OH)2D3导致生长抑制作用相对于单独使用铂类药物有轻微至显著的增强。这些相互作用的强度与铂类药物的剂量呈反比。用等效线图评估药物相互作用表明，在接近血清水平时，卡铂或顺铂与1,25(OH)2D3协同作用以抑制MCF - 7细胞生长。我们的研究结果表明，将生物修饰剂1,25(OH)2D3与细胞毒性药物联合用于治疗恶性疾病具有潜在的应用价值。
