skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy

Abstract

Radiotherapy is a widely used treatment for many tumors. Combination therapy using anti-angiogenic agents and radiation has shown promise; however, these combined therapies are reported to have many limitations in clinical trials. Here, we show that radiation transformed tumor endothelial cells (ECs) to fibroblasts, resulting in reduced vascular endothelial growth factor (VEGF) response and increased Snail1, Twist1, Type I collagen, and transforming growth factor (TGF)-β release. Irradiation of radioresistant Lewis lung carcinoma (LLC) tumors greater than 250 mm{sup 3} increased collagen levels, particularly in large tumor vessels. Furthermore, concomitant sunitinib therapy did not show a significant difference in tumor inhibition versus radiation alone. Thus, we evaluated multimodal therapy that combined pirfenidone, an inhibitor of TGF-induced collagen production, with radiation and sunitinib treatment. This trimodal therapy significantly reduced tumor growth, as compared to radiation alone. Immunohistochemical analysis revealed that radiation-induced collagen deposition and tumor microvessel density were significantly reduced with trimodal therapy, as compared to radiation alone. These data suggest that combined therapy using pirfenidone may modulate the radiation-altered tumor microenvironment, thereby enhancing the efficacy of radiation therapy and concurrent chemotherapy. - Highlights: • Radiation changes tumor endothelial cells to fibroblasts. • Radio-resistant tumors contain collagen deposits, especially in tumor vessels. •more » Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy. • Pirfenidone reduces radiation-induced collagen deposits in tumors.« less

Authors:
; ; ; ;
Publication Date:
OSTI Identifier:
22462093
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 462; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARCINOMAS; CHEMOTHERAPY; COLLAGEN; COMBINED THERAPY; COMPARATIVE EVALUATIONS; DENSITY; DEPOSITION; DEPOSITS; FIBROBLASTS; GROWTH FACTORS; INHIBITION; IRRADIATION; LUNGS; PLANT GROWTH; RADIOSENSITIVITY; RADIOTHERAPY

Citation Formats

Choi, Seo-Hyun, Nam, Jae-Kyung, Jang, Junho, Lee, Hae-June, and Lee, Yoon-Jin. Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.04.107.
Choi, Seo-Hyun, Nam, Jae-Kyung, Jang, Junho, Lee, Hae-June, & Lee, Yoon-Jin. Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy. United States. doi:10.1016/J.BBRC.2015.04.107.
Choi, Seo-Hyun, Nam, Jae-Kyung, Jang, Junho, Lee, Hae-June, and Lee, Yoon-Jin. Fri . "Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy". United States. doi:10.1016/J.BBRC.2015.04.107.
@article{osti_22462093,
title = {Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy},
author = {Choi, Seo-Hyun and Nam, Jae-Kyung and Jang, Junho and Lee, Hae-June and Lee, Yoon-Jin},
abstractNote = {Radiotherapy is a widely used treatment for many tumors. Combination therapy using anti-angiogenic agents and radiation has shown promise; however, these combined therapies are reported to have many limitations in clinical trials. Here, we show that radiation transformed tumor endothelial cells (ECs) to fibroblasts, resulting in reduced vascular endothelial growth factor (VEGF) response and increased Snail1, Twist1, Type I collagen, and transforming growth factor (TGF)-β release. Irradiation of radioresistant Lewis lung carcinoma (LLC) tumors greater than 250 mm{sup 3} increased collagen levels, particularly in large tumor vessels. Furthermore, concomitant sunitinib therapy did not show a significant difference in tumor inhibition versus radiation alone. Thus, we evaluated multimodal therapy that combined pirfenidone, an inhibitor of TGF-induced collagen production, with radiation and sunitinib treatment. This trimodal therapy significantly reduced tumor growth, as compared to radiation alone. Immunohistochemical analysis revealed that radiation-induced collagen deposition and tumor microvessel density were significantly reduced with trimodal therapy, as compared to radiation alone. These data suggest that combined therapy using pirfenidone may modulate the radiation-altered tumor microenvironment, thereby enhancing the efficacy of radiation therapy and concurrent chemotherapy. - Highlights: • Radiation changes tumor endothelial cells to fibroblasts. • Radio-resistant tumors contain collagen deposits, especially in tumor vessels. • Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy. • Pirfenidone reduces radiation-induced collagen deposits in tumors.},
doi = {10.1016/J.BBRC.2015.04.107},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 462,
place = {United States},
year = {2015},
month = {6}
}