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Authors
Miyake, Naomi Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine
Chikumi, Hiroki Division of Infectious Diseases, Tottori University Hospital
Yamaguchi, Kosuke Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine
Takata, Miyako Department of Pathobiological Science and Technology, School of Health Science, Tottori University Faculty of Medicine
Takata, Miki Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine Tottori University Researchers
Okada, Kensaku Division of Infectious Diseases, Tottori University Hospital
Kitaura, Tsuyoshi Division of Infectious Diseases, Tottori University Hospital
Nakamoto, Masaki Division of Infectious Diseases, Tottori University Hospital Tottori University Researchers KAKEN Search Researchers
Yamasaki, Akira Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine Tottori University Researchers KAKEN Search Researchers
Keywords
cetuximab
EGFR siRNA
KRAS
nonsmall cell lung cancer
Abstract
Background The epidermal growth factor receptor (EGFR) is a therapeutic target for patients with non-small cell lung cancer (NSCLC). Cetuximab is an anti-EGFR monoclonal antibody that inhibits EGFR signaling and proliferation of colorectal cancer and head and neck cancers. Since only few NSCLC patients benefit from cetuximab therapy, we evaluated a novel combination treatment using cetuximab and EGFR small interfering RNA (siRNA) to strongly suppress EGFR signaling and searched for a biomarker in NSCLC cell lines harboring wild-type EGFR.

Methods Alterations in EGFR and its downstream genes in five NSCLC cell lines (A549, Lu99, 86-2, Sq19 and Ma10) were assessed through sequencing. The protein expression levels of these molecules were assessed through western blotting. The effect of combination treatment was determined through cell proliferation assay, caspase-3/7 assay, invasion assay, and migration assay.

Results All cell lines were harboring wild-type EGFR, whereas KRAS, PTEN, TP53 and TP53 were mutated in A549 and Lu99; Lu99 and Sq19; Lu99, 86-2, Sq19 and Ma10; and A549, 86-2, and Sq19 cell lines, respectively. PTEN was not expressed in Sq19, and LKB1 was not expressed in both A549 and Sq19. TP53 was not expressed in both A549 and Lu99. The combination of cetuximab and EGFR siRNA significantly suppressed cell proliferation in 86-2, Sq19 and Ma10, which express wild-type KRAS. It induced apoptosis in A549, 86-2 and Ma10 cells, which express wild type PTEN. The combination treatment had no effect either on cell invasion nor migration in all cell lines.

Conclusion EGFR targeted therapy using the combination of cetuximab and EGFR siRNA is effective in NSCLC cell lines harboring wild-type EGFR. Wild-type KRAS may act as a potential biomarker for response to combination treatment by the induction of apoptosis in cells with wild-type PTEN.
Publisher
Tottori University Medical Press
Content Type
Journal Article
Link
ISSN・ISBN
05135710
NCID
AA00892882
Journal Title
Yonago Acta Medica
Current Journal Title
Yonago Acta Medica
Volume
62
Issue
1
Start Page
85
End Page
93
Published Date
2019-03-28
Publisher-DOI
Text Version
Publisher
Rights
注があるものを除き、この著作物は日本国著作権法により保護されています。 / This work is protected under Japanese Copyright Law unless otherwise noted.
Citation
Yonago Acta Medica. 2019, 62(1), 85-93
Department
Faculty of Medicine/Graduate School of Medical Sciences/University Hospital
Language
English