FGF-2 and HGF reverse abiraterone’s effect οn intracellular levels of DHT in androgen-dependent and androgen independent prostate cancer cell lines

Abstract

Purpose: Growth factors such as fibroblast growth factor 2 (FGF-2) and hepatocyte growth factor (HGF) appear at high levels in prostate cancer (PC). Abiraterone is an androgen biosynthesis inhibitor which is currently in use as a standard treatment in clinics to impair tumor growth. Development of resistance to anticancer therapies is unfortunately a very common feature of cancer cells that threatens the patient lives. This study aimed to investigate whether FGF-2 and HGF act as a possible resistant mechanism to the abiraterone activity on the androgen synthesis pathway in PC. Methods: The intracellular levels of 17-OH progesterone and dihydrotestosterone (DHT) were determined by enzyme immunoassays in cell lysates of LNCaP and PC3 PC cells upon co-treatment of cells with abiraterone and FGF-2 or HGF. Results: Abiraterone treatment resulted in significant reduction in the intracellular levels of 17-OH progesterone and DHT in both LnCap and PC3 cells. FGF-2 and HGF were found to decrease the intracellular levels of 17-OH progesterone in both cell lines, whereas HGF alone was found to increase the intracellular levels of DHT only in PC3 cells. However, the simultaneous exposure of cells to abiraterone and FGF-2 or HGF was found to result in an increase in the intracellular levels of DHT, while it did not result in changes in the intracellular levels of 17-OH progesterone. Conclusion: These findings suggest that FGF-2 and HGF may act as an escape mechanism, aiding the development of resistance to abiraterone by restoring intra-tumoral androgen synthesis that may contribute to disease progression. © 2020 Zerbinis Publications. All rights reserved.