Oncotarget

Research Papers: Pathology:

Silibinin attenuates radiation-induced intestinal fibrosis and reverses epithelial-to-mesenchymal transition

Joong Sun Kim, Na-Kyung Han, Sung-Ho Kim and Hae-June Lee _

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Oncotarget. 2017; 8:69386-69397. https://doi.org/10.18632/oncotarget.20624

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Abstract

Joong Sun Kim1, Na-Kyung Han2, Sung-Ho Kim3 and Hae-June Lee2

1 Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, Korea

2 Division of Basic Radiation Bioscience, Korea Institute of Radiological and Medical Sciences, Seoul, Korea

3 College of Veterinary Medicine, Chonnam National University, Gwangju, Korea

Correspondence to:

Hae-June Lee, email:

Keywords: silibinin, fibrosis, EMT, TGF-β1, radiation, Pathology Section

Received: July 12, 2017 Accepted: August 26, 2017 Published: September 02, 2017

Abstract

Radiotherapy is a common treatment for cancer patients, but its use is often restricted by the tolerance of normal tissue. As cancer patients live longer, delayed radiation effects on normal tissue have become a concern. Radiation-induced enteropathy, including inflammatory bowel disease and fibrosis, are major issues for long-term cancer survivors. To investigate whether silibinin attenuates delayed radiation-induced intestinal injury in mice, we focused on intestinal fibrotic changes. Silibinin improved delayed radiation injuries in mice in association with decreased collagen deposition within the intestines and deceased transforming growth factor (TGF)-β1 levels in the intestine and plasma. Treating mice bearing CT26 mouse colon cancer tumors with both silibinin and radiation stimulated tumor regression more than radiation alone. We also investigated the effect of silibinin on the radiation-induced epithelial-to-mesenchymal transition (EMT), the primary mechanism of fibrosis. We assessed changes in E-cadherin, N-cadherin, and α-smooth muscle actin expression, and demonstrated that silibinin attenuates radiation-induced EMT. Irradiating intestinal epithelial cells increased TGF-β1 levels, but silibinin suppressed TGF-β1 expression by inhibiting Smad2/3 phosphorylation. These results suggest silibinin has the potential to serve as a useful therapeutic agent in patients with radiation-induced intestinal fibrosis.


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