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Combined Effects of 1,25-Dihydroxyvitamin D₃ and Platinum Drugs on the Growth of MCF-7 Cells

Departments of Obstetrics and Gynecology [C. C., G. D., V. K. M., J. M. M., D. E. S.] and Pathology [W. D. L.], Wayne State University School of Medicine, Detroit, Michigan 48201, and Department of Obstetrics and Gynecology [Y. L. C.], Kyung-pook National University Hospital, Taegu, Republic of Korea 700-412

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 µg/ml of cis-diammine-1,1-cyclobutane dicarboxylatoplatinum(II) (carboplatin) were slightly less than those induced by 0.02 to 20 µg/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 µg/ml) or cisplatin (20 to 0.02 µg/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.

¹ Y. L. C. was a Visiting Scholar at Wayne State University, Detroit, MI while this work was being carried out.

² To whom requests for reprints should be addressed.

Received 8/24/90. Accepted 3/13/91.

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