Introduction

The combination of radiotherapy with bicalutamide is the standard treatment of prostate cancer patients with high-risk or locally advanced disease. Whether new-generation anti-androgens, like apalutamide, can improve the radio-curability of these patients is an emerging challenge.

Materials and 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.

中文翻译：

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阿帕他胺对前列腺癌的放射增敏作用

介绍

放疗联合比卡鲁胺是高危或局部晚期前列腺癌患者的标准治疗。新一代抗雄激素药物（如阿帕他胺）能否提高这些患者的放射治疗能力是一项新兴挑战。

材料和方法

我们比较检查了阿帕他胺和比卡鲁胺在激素敏感 (22Rv1) 和激素抗性 (PC3、DU145) 前列腺癌细胞系中的放射增敏活性。对 22Rv1 细胞系进行了异种移植实验。

结果

辐射剂量反应生存力和克隆形成测定表明，apalutamide 对所有三种细胞系均具有更强的放射增敏活性。γH2Ax 的共聚焦成像显示阿帕鲁胺和比卡鲁胺具有相似的 DNA 双链断裂修复动力学。在细胞凋亡途径中没有发现差异。当放疗与阿帕他胺联合使用时，一种引人注目的细胞死亡模式涉及 G1/S 期的核核破裂和细胞固缩。在 SCID 和 R2G2 小鼠体内进行的体内实验显示，当与阿帕他胺联合使用时，放疗（2 和 4 Gy）的疗效显着提高，导致广泛的异种移植物坏死。

结论

体外和体内实验支持阿帕他胺优于比卡鲁胺联合放疗治疗前列腺癌。鼓励开展临床研究以证明用阿帕鲁胺替代比卡鲁胺是否可以提高治愈率。