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Foretinib Enhances the Radiosensitivity in Esophageal Squamous Cell Carcinoma by Inhibiting Phosphorylation of c-Met

As a crucial event involved in the metastasis and relapse of esophageal cancer, c-Met overexpression has been considered as one of the culprits responsible for the failure in patients who received radiochemotherapy. Since c-Met has been confirmed to be pivotal for cell survival, proliferation and mi...

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Autores principales: Chen, Guang-Zong, Dai, Wang-Shu, Zhu, Hong-Cheng, Song, Hong-Mei, Yang, Xi, Wang, Yuan-Dong, Min, Hua, Lu, Qian, Liu, Shu, Sun, Xin-Chen, Zeng, Xiao-Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436250/
https://www.ncbi.nlm.nih.gov/pubmed/28529610
http://dx.doi.org/10.7150/jca.18135
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author Chen, Guang-Zong
Dai, Wang-Shu
Zhu, Hong-Cheng
Song, Hong-Mei
Yang, Xi
Wang, Yuan-Dong
Min, Hua
Lu, Qian
Liu, Shu
Sun, Xin-Chen
Zeng, Xiao-Ning
author_facet Chen, Guang-Zong
Dai, Wang-Shu
Zhu, Hong-Cheng
Song, Hong-Mei
Yang, Xi
Wang, Yuan-Dong
Min, Hua
Lu, Qian
Liu, Shu
Sun, Xin-Chen
Zeng, Xiao-Ning
author_sort Chen, Guang-Zong
collection PubMed
description As a crucial event involved in the metastasis and relapse of esophageal cancer, c-Met overexpression has been considered as one of the culprits responsible for the failure in patients who received radiochemotherapy. Since c-Met has been confirmed to be pivotal for cell survival, proliferation and migration, little is known about its impact on the regulation of radiosensitivity in esophageal cancer. The present study investigated the radiosensitization effects of c-Met inhibitor foretinib in ECA-109 and TE-13 cell lines. Foretinib inhibited c-Met signaling in a dose-dependent manner resulting in decreases in the cell viability of ECA-109 and TE-13. Pretreatment with foretinib synergistically prompted cell apoptosis and G2/M arrest induced by irradiation. Moreover, decreases ability of DNA damage repair was also observed. In vivo studies confirmed that the combinatorial use of foretinib with irradiation significantly diminishes tumor burden compared to either treatment alone. The present findings implied a crucial role of c-Met in the modulation of radiosensitization in esophageal cancer, and foretinib increased the radiosensitivity in ECA-109 and TE-13 cells mainly via c-Met signaling, highlighting a novel profile of foretinib as a potential radiosensitizer for the treatment of esophageal cancer.
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spelling pubmed-54362502017-05-19 Foretinib Enhances the Radiosensitivity in Esophageal Squamous Cell Carcinoma by Inhibiting Phosphorylation of c-Met Chen, Guang-Zong Dai, Wang-Shu Zhu, Hong-Cheng Song, Hong-Mei Yang, Xi Wang, Yuan-Dong Min, Hua Lu, Qian Liu, Shu Sun, Xin-Chen Zeng, Xiao-Ning J Cancer Research Paper As a crucial event involved in the metastasis and relapse of esophageal cancer, c-Met overexpression has been considered as one of the culprits responsible for the failure in patients who received radiochemotherapy. Since c-Met has been confirmed to be pivotal for cell survival, proliferation and migration, little is known about its impact on the regulation of radiosensitivity in esophageal cancer. The present study investigated the radiosensitization effects of c-Met inhibitor foretinib in ECA-109 and TE-13 cell lines. Foretinib inhibited c-Met signaling in a dose-dependent manner resulting in decreases in the cell viability of ECA-109 and TE-13. Pretreatment with foretinib synergistically prompted cell apoptosis and G2/M arrest induced by irradiation. Moreover, decreases ability of DNA damage repair was also observed. In vivo studies confirmed that the combinatorial use of foretinib with irradiation significantly diminishes tumor burden compared to either treatment alone. The present findings implied a crucial role of c-Met in the modulation of radiosensitization in esophageal cancer, and foretinib increased the radiosensitivity in ECA-109 and TE-13 cells mainly via c-Met signaling, highlighting a novel profile of foretinib as a potential radiosensitizer for the treatment of esophageal cancer. Ivyspring International Publisher 2017-03-12 /pmc/articles/PMC5436250/ /pubmed/28529610 http://dx.doi.org/10.7150/jca.18135 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Chen, Guang-Zong
Dai, Wang-Shu
Zhu, Hong-Cheng
Song, Hong-Mei
Yang, Xi
Wang, Yuan-Dong
Min, Hua
Lu, Qian
Liu, Shu
Sun, Xin-Chen
Zeng, Xiao-Ning
Foretinib Enhances the Radiosensitivity in Esophageal Squamous Cell Carcinoma by Inhibiting Phosphorylation of c-Met
title Foretinib Enhances the Radiosensitivity in Esophageal Squamous Cell Carcinoma by Inhibiting Phosphorylation of c-Met
title_full Foretinib Enhances the Radiosensitivity in Esophageal Squamous Cell Carcinoma by Inhibiting Phosphorylation of c-Met
title_fullStr Foretinib Enhances the Radiosensitivity in Esophageal Squamous Cell Carcinoma by Inhibiting Phosphorylation of c-Met
title_full_unstemmed Foretinib Enhances the Radiosensitivity in Esophageal Squamous Cell Carcinoma by Inhibiting Phosphorylation of c-Met
title_short Foretinib Enhances the Radiosensitivity in Esophageal Squamous Cell Carcinoma by Inhibiting Phosphorylation of c-Met
title_sort foretinib enhances the radiosensitivity in esophageal squamous cell carcinoma by inhibiting phosphorylation of c-met
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436250/
https://www.ncbi.nlm.nih.gov/pubmed/28529610
http://dx.doi.org/10.7150/jca.18135
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