@Article{096504016X14570992647087,
AUTHOR = {Yifan Zhao, Longxiao Wang, Qianyi Huang, Youqin Jiang, Jingdong Wang, Liyuan Zhang, Ye Tian, Hongying Yang},
TITLE = {Radiosensitization of Non-Small Cell Lung Cancer Cells by Inhibition of TGF-β1 Signaling With SB431542 Is Dependent on p53 Status},
JOURNAL = {Oncology Research},
VOLUME = {24},
YEAR = {2016},
NUMBER = {1},
PAGES = {1--7},
URL = {http://www.techscience.com/or/v24n1/56604},
ISSN = {1555-3906},
ABSTRACT = {Although medically inoperable patients with stage I non-small cell lung cancer cells (NSCLC) are often treated with 
stereotactic body radiation therapy, its efficacy can be compromised due to poor radiosensitivity of cancer cells. 
Inhibition of transforming growth factor-β1 (TGF-β1) using LY364947 and LY2109761 has been demonstrated to 
radiosensitize cancer cells such as breast cancer, glioblastoma, and lung cancer. Our previous results have demonstrated that another potent and selective inhibitor of TGF-β1 receptor kinases, SB431542, could radiosensitize H460 
cells both in vitro and in vivo. In the present study, we investigated whether SB431542 could radiosensitize other 
NSCLC cell lines, trying to explore the potential implication of this TGF-β1 inhibitor in radiotherapy for NSCLC 
patients. The results showed that A549 cells were significantly radiosensitized by SB431542, whereas no radiosensitizing effect was observed in H1299 cells. Interestingly, both H460 and A549 cells have wild-type p53, while H1299 
cells have deficient p53. To study whether the radiosensitizing effect of SB431542 was associated with p53 status of 
cancer cells, the p53 of H460 cells was silenced using shRNA transfection. Then it was found that the radiosensitizing effect of SB431542 on H460 cells was not observed in H460 cells with silenced p53. Moreover, X-irradiation 
caused rapid Smad2 activation in H460 and A549 cells but not in H1299 and H460 cells with silenced p53. The 
Smad2 activation postirradiation could be abolished by SB431542. This may explain the lack of radiosensitizing 
effect of SB431542 in H1299 and H460 cells with silenced p53. Thus, we concluded that the radiosensitizing effect 
of inhibition of TGF-β1 signaling in NSCLC cells by SB431542 was p53 dependent, suggesting that using TGF-β1 
inhibitor in radiotherapy may be more complicated than previously thought and may need further investigation.},
DOI = {10.3727/096504016X14570992647087}
}