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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2017
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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. |
format | Online Article Text |
id | pubmed-5436250 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
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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