Combined α-methylacyl-CoA racemase inhibition and docetaxel treatment reduce cell proliferation and decrease expression of heat shock protein 27 in androgen-receptor-variant-7-positive-prostate cancer cells

Abstract Background Disease progression in castrate-resistant prostate cancer (CRPC) is most commonly driven by the reactivation of androgen receptor (AR) signaling and involves AR splice variants including ARV7. Methods We used the ARV7-positive prostate cancer (PCa) cell line, 22Rv1, to study the relationship of the PCa marker α-methylacyl-CoA racemase (AMACR), AR and ARV7 in prostate cancer. Results Docetaxel addition but not AMACR inhibition decreased the proliferation of 22Rv1 cells. The combination of AMACR inhibition and docetaxel treatment resulted in a maximum reduction of cell proliferation. Western blotting analysis revealed that both AR and ARV7 expression were significantly decreased with the use of charcoal-stripped serum (CSS) following AMACR inhibition and docetaxel treatment. AMACR inhibition and docetaxel treatment in the CSS condition reduced the proliferation of 22Rv1, possibly via the downregulation of the heat shock protein 27 (HSP27). Conclusion Using cell proliferation and Western blot analysis, we demonstrated that AMACR inhibition and docetaxel treatment, under androgen deprivation conditions, significantly reduced the proliferation of ARV7 positive cancer cells and decreased the levels of AR and ARV7 expression, possibly via downregulation of HSP27.