+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Hepatocyte growth factor reduces sensitivity to the epidermal growth factor receptor-tyrosine kinase inhibitor, gefitinib, in lung adenocarcinoma cells harboring wild-type EGFR



Hepatocyte growth factor reduces sensitivity to the epidermal growth factor receptor-tyrosine kinase inhibitor, gefitinib, in lung adenocarcinoma cells harboring wild-type EGFR



Oncotarget 7(13): 16273-16281



Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy is an option for lung cancers harboring wild-type EGFR when chemotherapeutic reagents have failed. In this study, we found that the EGFR-TKI, gefitinib, modestly suppressed proliferation of the lung cancer cell lines, A549 and H358, which both harbor wild-type EGFR. Treatment with hepatocyte growth factor (HGF) reduced the sensitivity to gefitinib, whereas sensitivity was restored by treatment with an HGF antibody, a MET inhibitor, or depletion of MET but not ErbB3 gene. Moreover, both PI3K/mTOR inhibitors and MEK inhibitors suppressed proliferation of A549 cells, whereas only PI3K/mTOR inhibitors effectively suppressed cell viability of EGFR mutant PC-9 cells. Our findings suggest that HGF reduced the gefitinib sensitivity through MET and downstream PI3K and MAPK pathways. Combined use of EGFR-TKI and MET inhibitors or inhibition of downstream signaling molecules might be a better second or third line choice for a group of patients with advanced lung cancer harboring wild-type EGFR.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 057982329

Download citation: RISBibTeXText

PMID: 26919104

DOI: 10.18632/oncotarget.7586


Related references

Combined epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor and chemotherapy in non-small-cell lung cancer: chemo-refractoriness of cells harboring sensitizing-EGFR mutations in the presence of gefitinib. Lung Cancer 82(2): 305-312, 2013

The Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer Harboring Wild-type Epidermal Growth Factor Receptor: A Meta-analysis of 25 RCTs. American Journal of Clinical Oncology 40(4): 362-369, 2017

Epidermal growth factor receptor tyrosine kinase inhibitors vs conventional chemotherapy in non-small cell lung cancer harboring wild-type epidermal growth factor receptor: a meta-analysis. JAMA 311(14): 1430-1437, 2014

Melatonin sensitizes H1975 non-small-cell lung cancer cells harboring a T790M-targeted epidermal growth factor receptor mutation to the tyrosine kinase inhibitor gefitinib. Cellular Physiology and Biochemistry 34(3): 865-872, 2014

Expression of insulin-like growth factor 1 receptor (IGF-1R) predicts poor responses to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer patients harboring activating EGFR mutations. Lung Cancer 87(3): 311-317, 2015

Phase I study of TAS-121, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with non-small-cell lung cancer harboring EGFR mutations. Investigational new Drugs 37(6): 1207-1217, 2019

Quantitative Tyrosine Phosphoproteomics of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor-treated Lung Adenocarcinoma Cells Reveals Potential Novel Biomarkers of Therapeutic Response. Molecular and Cellular Proteomics 16(5): 891-910, 2017

Re-treatment with epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)for lung adenocarcinoma. Gan to Kagaku Ryoho. Cancer and ChemoTherapy 37(10): 1907-1911, 2010

Advanced lung adenocarcinoma harboring a mutation of the epidermal growth factor receptor: CT findings after tyrosine kinase inhibitor therapy. Radiology 270(2): 574-582, 2014

Epidermal growth factor receptor tyrosine kinase inhibitor treatment in patients with EGFR wild-type non-small-cell lung cancer: the never-ending story. Journal of Clinical Oncology 31(26): 3291-3293, 2013

Inhibition of cell cycle progression and invasion of cells expressing epidermal growth factor receptor but not mutant EGFR variant III by the specific EGFR tyrosine kinase inhibitor gefitinib. Proceedings of the American Association for Cancer Research Annual Meeting 44: 1238, 2003

Hepatocyte growth factor reduces susceptibility to an irreversible epidermal growth factor receptor inhibitor in EGFR-T790M mutant lung cancer. Clinical Cancer Research 16(1): 174-183, 2010

Proteomic signature corresponding to the response to gefitinib (Iressa, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor in lung adenocarcinoma. Clinical Cancer Research 13(3): 799-805, 2007

Cytokeratin 19 fragment predicts the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor in non-small-cell lung cancer harboring EGFR mutation. Journal of Thoracic Oncology 8(7): 892-898, 2013

Phase II study of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), and celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, in patients with platinum refractory non-small cell lung cancer (NSCLC). Journal of Thoracic Oncology 2(4): 299-305, 2007