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1,25-Dihydroxyvitamin D₃ and Platinum Drugs Act Synergistically to Inhibit the Growth of Prostate Cancer Cell Lines¹

Department of Pathology, University of Colorado Health Sciences Center, Denver, Colorado 80206

The majority of men who die from prostate cancer (PC) have hormone-refractory disease. To date, chemotherapeutic agents have had little or no impact on the survival of such patients. To explore a new approach for the treatment of hormone-refractory PC, we examined the combination effects of cis- or carboplatin with vitamin D. 1,25-Dihydroxyvitamin D₃ (1,25(OH)₂D₃) and its synthetic analogue, Ro 25-6760, have an antiproliferative effect on some prostate cancer cell lines. Consequently, the growth-inhibitory effects of the drugs were measured, both singularly and in combination with cis- or carboplatin, on PC cells. Our results show that although each of the drugs alone displayed antiproliferative activity, the growth inhibition of PC cells was further enhanced by the combination of 1,25(OH)₂D₃ or Ro 25-6760 and either platinum agent. The greatest enhancement of inhibition occurred using smaller concentrations of the platinum compound in combination with higher concentrations of 1,25(OH)₂D₃. Isobologram analysis revealed that 1,25(OH)₂D₃ and platinum acted in a synergistic manner to inhibit the growth of PC cells. Our findings suggest that there is potential clinical value in combining 1,25(OH)₂D₃ with platinum compounds for the treatment of advanced-stage human PC.

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