Conclusions
In vitro and in vivo experiments support the superiority of apalutamide over bicalutamide in combination with radiotherapy in prostate cancer. Clinical studies are encouraged to show whether replacement of bicalutamide with apalutamide may improve the curability rates.
Methods
We comparatively examined the radio-sensitising activity of apalutamide and bicalutamide in hormone-sensitive (22Rv1) and hormone-resistant (PC3, DU145) prostate cancer cell lines. Experiments with xenografts were performed for the 22Rv1 cell line.
Results
Radiation dose-response viability and clonogenic assays showed that apalutamide had a stronger radio-sensitising activity for all three cell lines. Confocal imaging for γΗ2Αx showed similar DNA double-strand break repair kinetics for apalutamide and bicalutamide. No difference was noted in the apoptotic pathway. A striking cell death pattern involving nuclear karyorrhexis and cell pyknosis in the G1/S phase was exclusively noted when radiation was combined with apalutamide. In vivo experiments in SCID and R2G2 mice showed significantly higher efficacy of radiotherapy (2 and 4 Gy) when combined with apalutamide, resulting in extensive xenograft necrosis. Conclusions: In vitro and in vivo experiments support the superiority of apalutamide over bicalutamide in combination with radiotherapy in prostate cancer. Clinical studies are encouraged to show whether replacement of bicalutamide with apalutamide may improve the curability rates.