Novel Combination Therapy of Prostate Cancer Cells With Arsenic Trioxide and Flutamide: An In-Vitro Study Publisher Pubmed



Mirzaei A¹ ; Akbari MR^{2, 3} ; Tamehri Zadeh SS¹ ; Khatami F¹ ; Mashhadi R¹ ; Aghamir SMK¹ Show Affiliations
Source: Tissue and Cell Published:2022

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. © 2021 Elsevier Ltd