Synergy of 1,25-dihydroxyvitamin D3 and carboplatin in growth suppression of SKOV-3 cells

1α,25-Dihydroxyvitamin D3 [1,25(OH)(2)D(3)] has been demonstrated to inhibit the growth of cancer cells. However, carboplatin is the most widely used chemotherapeutic agent to treat cancer. We hypothesized that vitamin D may enhance the antiproliferative effects of carboplatin, and tested this hypothesis in ovarian cancer SKOV-3 cells treated with carboplatin and 1,25(OH)(2)D(3). Cell viability was determined by Cell Counting Kit-8, while cell cycle distribution, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were analyzed by flow cytometry. In these experiments, 1,25(OH)(2)D(3) and carboplatin each provided dose-dependent suppression of SKOV-3 growth, and synergy was demonstrated between 10 nM 1,25(OH)(2)D(3) and carboplatin. The proportion of cells in G(0)/G(1) phase was markedly reduced by the drug combination, while the proportion of cells in G(2)/M phase was increased. Apoptosis did not increase in ovarian cancer cells treated with 10 nM 1,25(OH)(2)D(3) alone; however, 1,25(OH)(2)D(3) evidently enhanced carboplatin-induced apoptosis. Similarly, ROS production was evidently higher and MMP was lower in cells treated with the two drugs than in those treated with each drug alone. The results suggested that 1,25(OH)(2)D(3) suppresses SKOV-3 growth and enhances the antiproliferative effect of carboplatin. The drugs function synergistically by inducing cell cycle arrest, increasing apoptosis and ROS production, and reducing MMP.