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FEBS Open Bio. 2018 Dec 6;9(1):82-91. doi: 10.1002/2211-5463.12552. eCollection 2019 Jan.

Identification of radiation-induced EndMT inhibitors through cell-based phenomic screening.

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Cancer Biology Laboratory Institut Pasteur Korea Seongnam-si Korea.
Assay Development and Screening Institut Pasteur Korea Seongnam-si Korea.
Medicinal Chemistry Institut Pasteur Korea Seongnam-si Korea.
Division of Radiation Effects Korea Institute of Radiological and Medical Sciences Seoul Korea.


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.


CHIR‐99021; endothelial‐to‐mesenchymal transition; ionizing radiation; nonsmall cell lung cancer; radiation‐induced pulmonary fibrosis; visual phenomic screening

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