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Transforming growth factor-\u03b2 (TGF-\u03b2) is a key signal messenger in fibrosis, which plays an important role in radiation-induced fibrosis and cancer stem cell (CSC) development, may be mediated through the generation of oxidative stress. This study was conducted to confirm the efficacy of vactosertib, a TGF-\u03b2\/ALK5 inhibitor, as a potent inhibitor in radiation-induced oxidative stress generation, fibrosis and CSC development. We used a 4T1-Luc allograft BALB\/c syngeneic mouse model and 4T1-Luc and MDA-MB-231 cells for histological analysis, qRT-PCR, western blotting, ROS analysis, mammosphere formation analysis, monolayer fluorescence imaging analysis. Radiotherapy induces TGF-\u03b2 signaling, oxidative stress markers (4-HNE, NOX2, NOX4, PRDX1, NRF2, HO-1, NQO-1), fibrosis markers (PAI-1, \u03b1-SMA, FIBRONECTIN, COL1A1), and CSC properties. However, combination therapy with vactosertib not only inhibits these radiation-induced markers and properties by blocking TGF-\u03b2 signaling, but also enhances the anticancer effect of radiation by reducing the volume of breast cancer. Therefore, these data suggest that vactosertib can effectively reduce radiation fibrosis and resistance in breast cancer treatment by inhibiting radiation-induced TGF-\u03b2 signaling and oxidative stress, fibrosis, and CSC.<\/jats:p>","DOI":"10.1038\/s41598-022-20050-9","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T12:04:06Z","timestamp":1664280246000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Radiotherapy-induced oxidative stress and fibrosis in breast cancer are suppressed by vactosertib, a novel, orally bioavailable TGF-\u03b2\/ALK5 inhibitor"],"prefix":"10.1038","volume":"12","author":[{"given":"Jiyoung","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwon","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilyoung","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yhun Yhong","family":"Sheen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,27]]},"reference":[{"issue":"6","key":"20050_CR1","first-page":"3752","volume":"40","author":"YS Ko","year":"2018","unstructured":"Ko, Y. 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