NDLI: Targeting human epidermal growth factor receptor 2 enhances radiosensitivity and reduces the metastatic potential of Lewis lung carcinoma cells

Content Provider	Springer Nature : BioMed Central
Author	Tien, Yun Tsai, Chiao-Ling Hou, Wei-Hsien Chiang, Yun Hsu, Feng-Ming Tsai, Yu-Chieh Cheng, Jason Chia-Hsien
Abstract	Background Sublethal radiation induces matrix metalloproteinase 9 (MMP-9)-mediated radioresistance in Lewis lung carcinoma (LLC) cells and their metastatic dissemination. We aim to determine if EGFR/HER2 activation associates with MMP-9-mediated radioresistance and invasiveness in irradiated LLC cells. Methods LLC cells were treated with erlotinib or afatinib followed by sublethal radiation. After irradiation, we examined the phosphorylation of EGFR/HER2 and MMP-9 expression. Colony formation assay determined if the kinase inhibitors sensitize LLC cells to radiation. Matrigel-coated Boyden chamber assay assessed cellular invasiveness. Resulting tumors of wild-type LLC cells or HER2 knock-down mutant cells were irradiated to induce pulmonary metastases. Results Afatinib more effectively sensitized LLC cells to radiation and decreased invasiveness by inhibiting phosphorylation of EGFR, HER2, Akt, ERK, and p38, and down-regulating MMP-9 when compared to erlotinib. Afatinib abolished radiation-induced lung metastases in vivo. Furthermore, LLC HER2 knock-down cells treated with radiation had growth inhibition. Conclusion Dual inhibition of radiation-activated EGFR and HER2 signaling by afatinib suppressed the proliferation and invasion of irradiated LLC cells. Increased radiosensitivity and decreased metastatic dissemination were observed by pharmacological or genetic HER2 inhibition in vivo. These findings indicate that HER2 plays a pivotal role in enhancing radioresistance and reducing metastatic potential of LLC cells.
Related Links	https://ro-journal.biomedcentral.com/counter/pdf/10.1186/s13014-020-01493-8.pdf
Ending Page	11
Page Count	11
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s13014-020-01493-8
Journal	Radiation Oncology
Issue Number	1
Volume Number	15
Language	English
Publisher	BioMed Central
Publisher Date	2020-03-06
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Radiotherapy Imaging Radiology Human epidermal growth factor receptor 2 Lung cancer Afatinib MMP-9
Content Type	Text
Resource Type	Article
Subject	Radiology, Nuclear Medicine and Imaging Oncology
Journal Impact Factor	3.3/2023
5-Year Journal Impact Factor	3.6/2023

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