1α,25-dihydroxyvitamin D3 and platinum drugs act synergistically to inhibit the growth of prostate cancer cell lines

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 alpha,25-Dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3) 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 alpha,25(OH)(2)D-3 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 alpha,25(OH)(2)D-3. Isobologram analysis revealed that 1 alpha,25(OH)(2)D-3 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 la,25(OH)(2)D-3 with platinum compounds for the treatment of advanced-stage human PC.