In Vitro Potentiation of 5-Fluorouracii-lnduced Cytotoxicity by Leucovorin in Human Bladder Cancer Cell Lines

Choi, Han Yong

Abstract

Several experimental and clinical studies have shown that leucovorin(LV) potentiate the antitumor effect of 5-fluorouracil(SFU) by biochemical modulation. LV increases the intracellular reduced folate, which stabilizes the 5FU metabolite 5-fluorodeoxyuridine monophosphate (FdUMP):thymidylate synthase(TS) complex, thus increasing the block in the DNA synthesis pathway. This present study was designed to analyze the cytotoxic effects of the combination of 5FU and LV in bladder cancer cell lines. We used two human bladder transitional cell cancer cell lines (DU4184 and DU4284): In vitro cytotoxicity was assessed by the colorimetric assay. Them was a substantial difference of 5FU cytotoxicity between two cell lines. DU4284 cells were 2-fold less sensitive to 5FU than DU4184 cells (mean IC50 : 0.43M+0.02 vs. 0.21+0.0l.uM). Enhanced cytotoxic effect of 5FU by coadministration of LV was seen in both cell lines with the greater degree of potentiation being observed in DU4284 cells (enhancement factor: 7.2 vs. 2.7 fold, respectively). It is concluded that, in this study, 1) bladder cancer cells reveal various patterns of cytotoxic responses to 5FU only, 2) LV significantly enhances the cytotoxicity of 5FU in bladder cancer cells including the 5FU- less sensitive cells. These data support the use of LV in combination with 5FU as adjuvant treatment of patients with advanced metastatic bladder cancer.