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

Zhang Z, Zhang H, Hu Z, Wang P, Wan J, Li B - Oncol Lett (2014)

Bottom Line: Apoptosis did not increase in ovarian cancer cells treated with 10 nM 1,25(OH)2D3 alone; however, 1,25(OH)2D3 evidently enhanced carboplatin-induced apoptosis.The results suggested that 1,25(OH)2D3 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Toxicology, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, P.R. China.

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)2D3 and carboplatin each provided dose-dependent suppression of SKOV-3 growth, and synergy was demonstrated between 10 nM 1,25(OH)2D3 and carboplatin. The proportion of cells in G0/G1 phase 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)2D3 alone; however, 1,25(OH)2D3 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)2D3 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.

No MeSH data available.


Related in: MedlinePlus

Combined effect of 1,25(OH)2D3 and carboplatin on cell cycle distribution. (A) G2/M cell cycle arrest in SKOV-3 cells treated with 1,25(OH)2D3 and carboplatin versus the untreated cells. */#P<0.05, vs. the vehicle controls. (B) Flow cytometric analysis: a, control group; b, 10-nM 1,25(OH)2D3 group; c, 40-mg/l carboplatin group; and d, combined treatment group. Similar results were obtained in all three experiments. 1,25(OH)2D3, 1,25-dihydroxyvitamin D3.
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f2-ol-08-03-1348: Combined effect of 1,25(OH)2D3 and carboplatin on cell cycle distribution. (A) G2/M cell cycle arrest in SKOV-3 cells treated with 1,25(OH)2D3 and carboplatin versus the untreated cells. */#P<0.05, vs. the vehicle controls. (B) Flow cytometric analysis: a, control group; b, 10-nM 1,25(OH)2D3 group; c, 40-mg/l carboplatin group; and d, combined treatment group. Similar results were obtained in all three experiments. 1,25(OH)2D3, 1,25-dihydroxyvitamin D3.

Mentions: To determine whether 1,25(OH)2D3 enhancement of the antiproliferative activity of carboplatin was due to alterations in the cell cycle, the cell cycle distribution of SKOV-3 cells treated with the vehicle control, 10 nM 1,25(OH)2D3, 40 mg/l of carboplatin and the drugs in combination were compared. Compared with the vehicle control, 1,25(OH)2D3 significantly increased the percentage of cells in G0/G1 phase, accompanied by a reduction of cells in G2/M phase. The reverse effect occurred with carboplatin; a decrease in cells in G0/G1 phase and an increase in cells in G2/M phase was observed. However, the percentage of cells in S phase changed very little. Following treatment with 10 nM 1,25(OH)2D3 and 40 mg/l carboplatin, the distribution of G0/G1-phase cells in SKOV-3 cells was further reduced, while cells in G2/M phase evidently increased (Fig. 2A and B). Therefore, it was concluded that the combined treatment had a similar effect as carboplatin treatment alone, but this observation regarding cell cycle arrest requires more consideration.


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

Zhang Z, Zhang H, Hu Z, Wang P, Wan J, Li B - Oncol Lett (2014)

Combined effect of 1,25(OH)2D3 and carboplatin on cell cycle distribution. (A) G2/M cell cycle arrest in SKOV-3 cells treated with 1,25(OH)2D3 and carboplatin versus the untreated cells. */#P<0.05, vs. the vehicle controls. (B) Flow cytometric analysis: a, control group; b, 10-nM 1,25(OH)2D3 group; c, 40-mg/l carboplatin group; and d, combined treatment group. Similar results were obtained in all three experiments. 1,25(OH)2D3, 1,25-dihydroxyvitamin D3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4114616&req=5

f2-ol-08-03-1348: Combined effect of 1,25(OH)2D3 and carboplatin on cell cycle distribution. (A) G2/M cell cycle arrest in SKOV-3 cells treated with 1,25(OH)2D3 and carboplatin versus the untreated cells. */#P<0.05, vs. the vehicle controls. (B) Flow cytometric analysis: a, control group; b, 10-nM 1,25(OH)2D3 group; c, 40-mg/l carboplatin group; and d, combined treatment group. Similar results were obtained in all three experiments. 1,25(OH)2D3, 1,25-dihydroxyvitamin D3.
Mentions: To determine whether 1,25(OH)2D3 enhancement of the antiproliferative activity of carboplatin was due to alterations in the cell cycle, the cell cycle distribution of SKOV-3 cells treated with the vehicle control, 10 nM 1,25(OH)2D3, 40 mg/l of carboplatin and the drugs in combination were compared. Compared with the vehicle control, 1,25(OH)2D3 significantly increased the percentage of cells in G0/G1 phase, accompanied by a reduction of cells in G2/M phase. The reverse effect occurred with carboplatin; a decrease in cells in G0/G1 phase and an increase in cells in G2/M phase was observed. However, the percentage of cells in S phase changed very little. Following treatment with 10 nM 1,25(OH)2D3 and 40 mg/l carboplatin, the distribution of G0/G1-phase cells in SKOV-3 cells was further reduced, while cells in G2/M phase evidently increased (Fig. 2A and B). Therefore, it was concluded that the combined treatment had a similar effect as carboplatin treatment alone, but this observation regarding cell cycle arrest requires more consideration.

Bottom Line: Apoptosis did not increase in ovarian cancer cells treated with 10 nM 1,25(OH)2D3 alone; however, 1,25(OH)2D3 evidently enhanced carboplatin-induced apoptosis.The results suggested that 1,25(OH)2D3 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Toxicology, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, P.R. China.

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)2D3 and carboplatin each provided dose-dependent suppression of SKOV-3 growth, and synergy was demonstrated between 10 nM 1,25(OH)2D3 and carboplatin. The proportion of cells in G0/G1 phase 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)2D3 alone; however, 1,25(OH)2D3 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)2D3 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.

No MeSH data available.


Related in: MedlinePlus