title: Synergy of 1,25-dihydroxyvitamin D3 and carboplatin in growth suppression of SKOV-3 cells.
abstract: 1α,25-Dihydroxyvitamin D3 [1,25(OH)2D3] 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)2D3. 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)2D3and carboplatin each provided dose-dependent suppression of SKOV-3 growth, and synergy was demonstrated between 10 nM 1,25(OH)2D3and carboplatin. The proportion of cells in G0/G1phase was markedly reduced by the drug combination, while the proportion of cells in G2/M phase was increased. Apoptosis did not increase in ovarian cancer cells treated with 10 nM 1,25(OH)2D3alone; however, 1,25(OH)2D3evidently 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)2D3suppresses 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.
authors.affiliation: Department of Toxicology, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Zengli
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Hemei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Li Shui Center for Disease Control and Prevention, Lishui, Zhejiang 323000, P.R. China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Toxicology, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Toxicology, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Toxicology, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Bingyan
authors.initials: B
authors.lastname: Li
keywords: 1,25-dihydroxyvitamin D3; SKOV-3 cells; carboplatin; ovarian cancer