ArticleRadiation oncology (London, England)2020
Targeting human epidermal growth factor receptor 2 enhances radiosensitivity and reduces the metastatic potential of Lewis lung carcinoma cells.
Article in Radiation oncology (London, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- HER2-specific synthetic antigen receptor T cell therapy synergizes with radiotherapy to provide improved antitumor efficacy in non-small cell lung cancer.Journal of leukocyte biology · 2026Article
- High-CD14-expressing urothelial cancer cells foster a neutrophil-rich tumor microenvironment that increases the risk of radiation-promoted distant metastasis.Journal of biomedical science · 2026Article
- Effect of afatinib combined with induction chemotherapy on primary tumor regression and safety of surgical margins in locally advanced oral cancer.American journal of translational research · 2026Article
- Coordination of anti-CTLA-4 with whole-brain radiation therapy decreases tumor burden during treatment in a novel syngeneic model of lung cancer brain metastasis.Cancer immunology, immunotherapy : CII · 2024Article
- Targeting EGFR in Combination with Nutritional Supplements on Antitumor Efficacy in a Lung Cancer Mouse Model.Marine drugs · 2022Article
- CircMAN1A2 promotes vasculogenic mimicry of nasopharyngeal carcinoma cells through upregulating ERBB2 via sponging miR-940.Oncology research · 2022Article
- Molecular Mechanisms of Specific Cellular DNA Damage Response and Repair Induced by the Mixed Radiation Field During Boron Neutron Capture Therapy.Frontiers in oncology · 2021Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSublethal 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.
methodsLLC 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.
resultsAfatinib 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.
conclusionDual 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.
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