Barrado Marta, Blanco-Luquin Idoia, Navarrete Paola Andrea, Visus Ignacio, Guerrero-Setas David, Escors David, Kochan Grazyna, Arias Fernando
Biomedical Research Center of Navarra-Navarrabiomed, Fundación Miguel Servet, IdISNA, Irunlarrea 3, 31008 Pamplona, Navarre, Spain.
Department of Radiation Oncology, Hospital of Navarre, IdISNA, Irunlarrea 3, 31008 Pamplona, Navarre, Spain.
Rep Pract Oncol Radiother. 2019 Mar-Apr;24(2):221-226. doi: 10.1016/j.rpor.2019.02.002. Epub 2019 Feb 22.
To evaluate the radiopotentiation of enzalutamide in human prostate cancer cells.
While radiotherapy is the first line of treatment for prostate cancer, androgen blockade therapies are demonstrating significant survival benefit as monotherapies. As androgen blockade can cause cell death by apoptosis, it is likely that androgen blockade will potentiate the cytotoxic activities of radiotherapy.
Here, we tested the potential synergistic effects of these two treatments over two human metastatic prostate cancer cells by real-time cell analysis (RTCA), androgen-sensitive LNCaP cells (Lymph Node Carcinoma of the Prostate) and androgen-independent PC-3. Both cell lines were highly resistant to high doses of radiotherapy.
A pre-treatment of LNCaP cells with IC50 concentrations of enzalutamide significantly sensitized them to radiotherapy through enhanced apoptosis. In contrast, enzalutamide resistant PC-3 cells were not sensitized to radiotherapy by androgen blockade.
These results provide evidence that the enzalutamide/radiotherapy combination could maximize therapeutic responses in patients with enzalutamide-sensitive prostate cancer.
评估恩杂鲁胺对人前列腺癌细胞的放射增敏作用。
虽然放射治疗是前列腺癌的一线治疗方法，但雄激素阻断疗法作为单一疗法显示出显著的生存益处。由于雄激素阻断可通过凋亡导致细胞死亡，雄激素阻断很可能会增强放射治疗的细胞毒性活性。
在此，我们通过实时细胞分析（RTCA）测试了这两种治疗方法对两种人转移性前列腺癌细胞的潜在协同作用，即雄激素敏感的LNCaP细胞（前列腺淋巴结癌）和雄激素非依赖性PC-3细胞。两种细胞系对高剂量放射治疗均具有高度抗性。
用IC50浓度的恩杂鲁胺预处理LNCaP细胞可通过增强凋亡使其对放射治疗显著敏感。相比之下，恩杂鲁胺耐药的PC-3细胞未因雄激素阻断而对放射治疗敏感。
这些结果提供了证据，表明恩杂鲁胺/放射治疗联合应用可使恩杂鲁胺敏感的前列腺癌患者的治疗反应最大化。
