Marta Barrado1,2, Idoia Blanco-Luquin1, Paola Andrea Navarrete2, Ignacio Visus2, David Guerrero-Setas1, David Escors1,3, Grazyna Kochan1, Fernando Arias2. 1. Biomedical Research Center of Navarra-Navarrabiomed, Fundación Miguel Servet, IdISNA, Irunlarrea 3, 31008 Pamplona, Navarre, Spain. 2. Department of Radiation Oncology, Hospital of Navarre, IdISNA, Irunlarrea 3, 31008 Pamplona, Navarre, Spain. 3. Department of Infection and Immunity, Rayne Institute, University College London, 5 University Street, WC1E 6JJ London, United Kingdom.
Abstract
AIM: To evaluate the radiopotentiation of enzalutamide in human prostate cancer cells. BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: These results provide evidence that the enzalutamide/radiotherapy combination could maximize therapeutic responses in patients with enzalutamide-sensitive prostate cancer.
AIM: To evaluate the radiopotentiation of enzalutamide in human prostate cancer cells. BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: These results provide evidence that the enzalutamide/radiotherapy combination could maximize therapeutic responses in patients with enzalutamide-sensitive prostate cancer.
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