Synergistic Impact Of Combined Zoledronic Acid / 5-FU And Zoledronic Acid / Flutamide On The Expression Of MiR-382, MiR-18a, Bcl - 2 And P53 In PC- 3 Cancer Cells.

Introduction/Aims: assessment of the chemotherapeutic effect of zoledronic acid (ZA) when combined with 5-FU or Flutamide on prostate cancer cell line (PC-3), through estimation of synergistic effects of combinations on cytotoxicity, expression of miRNAs and apoptosis. Methods: cell viability was assessed by MTT assay. Different concentrations of combined ZA/5-FU and ZA/Flutamide were applied to PC-3 and were compared to single drug treatment for 48 h. Changes in miR-18a and miR-382 expressions after treatment were determined using quantitative real time-polymerase chain reaction (qRT-PCR). Immunofluorescence staining analysis was used to assess the changes in Bcl-2 and p53 expression. Results: IC50 of ZA, 5-FU, and Flutamide was 13.47 μM, 8.23 μM and 9.42 μM respectively. While the combination index (CI) of ZA/5-FU and ZA/Flutamide reached a level of synergistic effects at the combination of ¼ IC50 of each. The combination therapy was associated with over-expression of miR-382, down-expression of miR-18a, reduced Bcl-2 and enhanced p53 expressions. Conclusion: ZA/5-FU and ZA/Flutamide combinations offer interesting chemotherapeutic effects with lower doses and synergistic effects more than treatment with single drugs to be further investigated.