Open AccessIdentification of radiation‐induced EndMT inhibitors through cell‐based phenomic screening
Author(s) -
Song Yeonhwa,
Lee SuYeon,
Kim ARam,
Kim Sanghwa,
Heo Jinyeong,
Shum David,
Kim SeHyuk,
Choi Inhee,
Lee YoonJin,
Seo Haeng Ran
Publication year - 2019
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12552
Subject(s) - umbilical vein , cell , fibrosis , cancer research , fibroblast , phenotype , mesenchymal stem cell , ionizing radiation , lung , microbiology and biotechnology , medicine , chemistry , biology , pathology , in vitro , biochemistry , irradiation , physics , nuclear physics , gene
Radiation‐induced pulmonary fibrosis (RIPF) triggers physiological abnormalities. Endothelial‐to‐mesenchymal transition (EndMT) is the phenotypic conversion of endothelial cells to fibroblast‐like cells and is involved in RIPF. In this study, we established a phenomic screening platform to measure radiation‐induced stress fibers and optimized the conditions for high‐throughput screening using human umbilical vein endothelial cells (HUVECs) to develop compounds targeting RIPF. The results of screening indicated that CHIR‐99021 reduced radiation‐induced fibrosis, as evidenced by an enlargement of cell size and increases in actin stress fibers and α‐smooth muscle actin expression. These effects were elicited without inducing serious toxicity in HUVECs, and the cytotoxic effect of ionizing radiation (IR) in nonsmall cell lung cancer was also enhanced. These results demonstrate that CHIR‐99021 enhanced the effects of IR therapy by suppressing radiation‐induced EndMT in lung cancer.