J Cancer 2017; 8(6):983-992. doi:10.7150/jca.18135

Research Paper

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

Guang-Zong Chen1*, Wang-Shu Dai1*, Hong-Cheng Zhu1*, Hong-Mei Song3, Xi Yang4, Yuan-Dong Wang1, Hua Min1, Qian Lu1, Shu Liu1, Xin-Chen Sun1✉, Xiao-Ning Zeng2✉

1. Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
2. Department of Respiratory & Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
3. Department of Radiation Oncology, Lianyungang NO.2 People's Hospital Affiliated to Bengbu Medical College, Lianyungang 222000, China
4. Department of Radiation Oncology, the Cancer Hospital of Fudan University, Shanghai 200000, China
* These authors contributed equally to this work.

Abstract

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.

Keywords: Foretinib, Esophageal cancer, Radiosensitivity, c-Met

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How to cite this article:
Chen GZ, Dai WS, Zhu HC, Song HM, Yang X, Wang YD, Min H, Lu Q, Liu S, Sun XC, Zeng XN. Foretinib Enhances the Radiosensitivity in Esophageal Squamous Cell Carcinoma by Inhibiting Phosphorylation of c-Met. J Cancer 2017; 8(6):983-992. doi:10.7150/jca.18135. Available from http://www.jcancer.org/v08p0983.htm