caa a22 4500 60554283X CHVBK 20210128100923.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00109-014-1206-6 doi (NATIONALLICENCE)springer-10.1007/s00109-014-1206-6 TGF-β1 mediates the radiation response of prostate cancer [Elektronische Daten] [Chun-Te Wu, Ching-Chuan Hsieh, Tzu-Chen Yen, Wen-Cheng Chen, Miao-Fen Chen] Radiotherapy is the main treatment modality for prostate cancer. This study investigated the role of TGF-β1 in biological sequelae and tumor regrowth following irradiation, which are critical for the clinical radiation response of prostate cancer. Human and murine prostate cancer cell lines, and corresponding hormone-refractory (HR) cells, were used to examine the radiation response by clonogenic assays in vitro and tumor growth delay in vivo. Biological changes after irradiation, including cell death and tumor regrowth, were examined by experimental manipulation of TGF-β1 signaling. The correlations among tumor radiation responses, TGF-β1 levels, and regulatory T cells (Tregs) recruitment were also evaluated using animal experiments. HR prostate cancer cells appeared more radioresistant and had higher expression of TGF-β1 compared to hormone-sensitive (HS) cells. TGF-β1 expression was positively linked to irradiation and radioresistance, as demonstrated by in vitro and in vivo experiments. Inhibition of TGF-β1 increased tumor inhibition and DNA damage after irradiation. When mice were irradiated with a sub-lethal dose, the regrowth of irradiated tumors was significantly correlated with TGF-β1 levels and Tregs accumulation in vivo. Furthermore, blocking TGF-β1 clearly attenuated Tregs accumulation and tumor regrowth following treatment. These data demonstrate that TGF-β1 is important in determining the radiation response of prostate cancer, including tumor cell killing and the tumor microenvironment. Therefore, concurrent treatment with a TGF-β1 inhibitor is a potential therapeutic strategy for increasing the radiation response of prostate cancer, particularly for more aggressive or HR cancer cells. Key message: • HR prostate cancer cells appeared more radioresistant and had higher expression of TGF-β1. • TGF-β1 was positively linked to the radiation resistance of prostate cancer. • Tumor regrowth following irradiation was significantly correlated with TGF-β1 and Tregs levels. • Blocking TGF-β1 significantly attenuated RT-induced DNA repair and Tregs. • TGF-β1 inhibitor increases the radiation response of HR cancer cells. Springer-Verlag Berlin Heidelberg, 2014 TGF-β1 nationallicence Irradiation nationallicence Regulatory T cells nationallicence Prostate cancer nationallicence Wu Chun-Te Department of Urology, Chang Gung Memorial Hospital, KeeLung, Taiwan aut Hsieh Ching-Chuan College of Medicine, Chang Gung University, Taoyuan, Taiwan aut Yen Tzu-Chen College of Medicine, Chang Gung University, Taoyuan, Taiwan aut Chen Wen-Cheng College of Medicine, Chang Gung University, Taoyuan, Taiwan aut Chen Miao-Fen College of Medicine, Chang Gung University, Taoyuan, Taiwan aut Journal of Molecular Medicine Springer Berlin Heidelberg 93/1(2015-01-01), 73-82 0946-2716 93:1<73 2015 93 109 https://doi.org/10.1007/s00109-014-1206-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00109-014-1206-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wu Chun-Te Department of Urology, Chang Gung Memorial Hospital, KeeLung, Taiwan aut NATIONALLICENCE 700 1- Hsieh Ching-Chuan College of Medicine, Chang Gung University, Taoyuan, Taiwan aut NATIONALLICENCE 700 1- Yen Tzu-Chen College of Medicine, Chang Gung University, Taoyuan, Taiwan aut NATIONALLICENCE 700 1- Chen Wen-Cheng College of Medicine, Chang Gung University, Taoyuan, Taiwan aut NATIONALLICENCE 700 1- Chen Miao-Fen College of Medicine, Chang Gung University, Taoyuan, Taiwan aut NATIONALLICENCE 773 0- Journal of Molecular Medicine Springer Berlin Heidelberg 93/1(2015-01-01), 73-82 0946-2716 93:1<73 2015 93 109