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oai:repository.lib.tottori-u.ac.jp:00004773 2023-09-28T23:55:03Z 1:9 2:12 23:34:993:994

Effect of Cetuximab and EGFR Small Interfering RNA Combination Treatment in NSCLC Cell Lines with Wild Type EGFR and Use of KRAS as a Possible Biomarker for Treatment Responsiveness Miyake, Naomi Chikumi, Hiroki Yamaguchi, Kosuke Takata, Miyako Takata, Miki タカタ, ミキ Takata, Miki Okada, Kensaku Kitaura, Tsuyoshi 70379642 Nakamoto, Masaki ナカモト, マサキ Nakamoto, Masaki 70325009 Yamasaki, Akira ヤマサキ, アキラ Yamasaki, Akira Miyake, Naomi Chikumi, Hiroki Yamaguchi, Kosuke Takata, Miyako Okada, Kensaku Kitaura, Tsuyoshi Yonago Acta medica　編集委員会 cetuximab EGFR siRNA KRAS nonsmall cell lung cancer cetuximab EGFR siRNA KRAS nonsmall cell lung cancer [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. Tottori University Medical Press 2019-03-28 eng journal article VoR https://repository.lib.tottori-u.ac.jp/records/4773 10.33160/yam.2019.03.012 Yonago Acta Medica. 2019, 62(1), 85-93 https://www.jstage.jst.go.jp/article/yam/62/1/62_2019.03.012/_article/-char/en https://www.jstage.jst.go.jp/article/yam/62/1/62_2019.03.012/_article/-char/en http://www.lib.tottori-u.ac.jp/yam/yam/yam62-1/62-1contents.html http://www.lib.tottori-u.ac.jp/yam/yam/yam62-1/62-1contents.html AA00892882 05135710 Yonago Acta Medica Yonago Acta Medica 62 1 85 93 https://repository.lib.tottori-u.ac.jp/record/4773/files/yam62(1)_85.pdf application/pdf 1.2 MB 2019-05-22