Vitamin D increases the efficacy of cisplatin on bladder cancer cell lines.

Abstract

1,25(OH)2D3(Calcitriol), which is a broad regulatory molecule, plays a role in changing the efficacy of chemotherapeutic drugs. Cisplatin is one of a current standard chemotherapy regimen for bladder cancer. Increasing the effectiveness of the treatment and reducing the side effects to chemotherapeutics are of great importance in bladder cancer. We aimed to investigate the effect of the combination of cisplatin and calcitriol in order to create a possible advantage in treatment of bladder cancer. T24, ECV-304 and HUVEC cell lines were treated with calcitriol and cisplatin individually and in combination. Dose determination and combination treatments of calcitriol and cisplatin were evaluated using the MTT assay for cytotoxicity analysis on the cells. Annexin V-PI staining method was used for apoptosis determination by flow cytometry. Also the P-gp expression levels were determined by flow cytometry. The combination treatment increased the anti-proliferative efficacy compared to the efficacy in cisplatin alone in T24 cells and reduced the cytotoxicity in the HUVEC healthy cells compared to cisplatin alone. Combination treatment achieved significantly higher apoptosis rate in T24 cells compared with the rates in treatment of cisplatin alone. However apoptosis decreased in HUVEC cell line. P-gp ratios were increased in HUVEC and decreased in T24 cells with combination treatment compared to the numbers in the control cells. The rate of apoptosis and P-gp levels showed no significant change in ECV-304 cells. Our study revealed that the combination of calcitriol and cisplatin allows the use of cisplatin at lower doses in T24 bladder cancer cell line.