Akram Mirzaei1, Mohammad Reza Akbari2, Seyed Saeed Tamehri Zadeh1, Fatemeh Khatami1, Rahil Mashhadi1, Seyed Mohammad Kazem Aghamir3. 1. Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran. 2. Women's College Research Institute, Women's College Hospital, University of Toronto, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Canada. 3. Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: mkaghamir@tums.ac.ir.
Abstract
OBJECTIVE: The study objective was to assess the therapeutic potential of Arsenic Trioxide (ATO) and Flutamide combination for metastatic prostate cancer (PCa) treatment. MATERIAL AND METHOD: LNCaP and PC3 cell lines were treated with different concentrations of ATO and PCa conventional drug Flutamide alone and/or in combination to find effective doses and IC50 values. Percentages of apoptotic cells were evaluated by Annexin/PI staining and the proliferative inhibitory effect was assessed by Micro Culture Tetrazolium Test (MTT). Expression of SNAIL, KLK2, E-cadherin, and angiogenesis genes (VEGFA and VEGFC), and apoptosis genes (Bcl2, and P53) were examined by real-time PCR. RESULTS: The combination of Flutamide and ATO significantly increased the percentage of apoptotic cells and inhibited PCa cells proliferation compared with each drug alone in LNCaP and PC3 cell lines. Generally, both cell lines treated with the combination of Flutamide and ATO showed a decrease in expression of KLK2, angiogenesis genes (VEGFA and VEGFC), and apoptosis gene (Bcl2), and an increase in expression of E-cadherin and P53 genes; however, contradictory findings were found regarding SNAIL expression in LNCaP and PC3 cells. CONCLUSION: The combination therapy with ATO and flutamide has augmented the anti-tumor effect on LNCaP and PC3 cells, which probably originates from their potential to induce apoptosis and inhibit the proliferation of PCa cells simultaneously.
OBJECTIVE: The study objective was to assess the therapeutic potential of Arsenic Trioxide (ATO) and Flutamide combination for metastatic prostate cancer (PCa) treatment. MATERIAL AND METHOD: LNCaP and PC3 cell lines were treated with different concentrations of ATO and PCa conventional drug Flutamide alone and/or in combination to find effective doses and IC50 values. Percentages of apoptotic cells were evaluated by Annexin/PI staining and the proliferative inhibitory effect was assessed by Micro Culture Tetrazolium Test (MTT). Expression of SNAIL, KLK2, E-cadherin, and angiogenesis genes (VEGFA and VEGFC), and apoptosis genes (Bcl2, and P53) were examined by real-time PCR. RESULTS: The combination of Flutamide and ATO significantly increased the percentage of apoptotic cells and inhibited PCa cells proliferation compared with each drug alone in LNCaP and PC3 cell lines. Generally, both cell lines treated with the combination of Flutamide and ATO showed a decrease in expression of KLK2, angiogenesis genes (VEGFA and VEGFC), and apoptosis gene (Bcl2), and an increase in expression of E-cadherin and P53 genes; however, contradictory findings were found regarding SNAIL expression in LNCaP and PC3 cells. CONCLUSION: The combination therapy with ATO and flutamide has augmented the anti-tumor effect on LNCaP and PC3 cells, which probably originates from their potential to induce apoptosis and inhibit the proliferation of PCa cells simultaneously.