Non‑small cell lung cancer PC‑9 cells exhibit increased sensitivity to gemcitabine and vinorelbine upon acquiring resistance to EGFR‑tyrosine kinase inhibitors

Hamamoto,Junko; Yasuda,Hiroyuki; Aizawa,Kaito; Nishino,Makoto; Nukaga,Shigenari; Hirano,Toshiyuki; Kawada,Ichiro; Naoki,Katsuhiko; Betsuyaku,Tomoko; Soejima,Kenzo

doi:10.3892/ol.2017.6591

Non‑small cell lung cancer PC‑9 cells exhibit increased sensitivity to gemcitabine and vinorelbine upon acquiring resistance to EGFR‑tyrosine kinase inhibitors

Authors:
- Junko Hamamoto
- Hiroyuki Yasuda
- Kaito Aizawa
- Makoto Nishino
- Shigenari Nukaga
- Toshiyuki Hirano
- Ichiro Kawada
- Katsuhiko Naoki
- Tomoko Betsuyaku
- Kenzo Soejima
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Affiliations: Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo 160‑8582, Japan, Keio University School of Medicine, Tokyo 160‑8582, Japan , Keio Cancer Center, Keio University Hospital, Tokyo 160‑0016, Japan
Published online on: July 18, 2017 https://doi.org/10.3892/ol.2017.6591
Pages: 3559-3565
Copyright: © Hamamoto et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Epidermal growth factor receptor (EGFR)‑tyrosine kinase inhibitors (EGFR‑TKIs) are widely used for the treatment of non‑small cell lung cancers (NSCLCs) harboring EGFR‑activating mutations. However, lung cancer cells inevitably acquire resistance to these EGFR‑TKIs. The majority of patients whose lung cancer acquires resistance to EGFR‑TKIs are subjected to treatment using cytotoxic agents. The present study aimed to determine if lung cancer cells acquiring resistance to EGFR‑TKIs also develop altered sensitivity to cytotoxic agents. It was revealed that lung cancer cells that had developed resistance to EGFR‑TKIs had increased sensitivity to gemcitabine and vinorelbine compared with EGFR‑TKI naïve cells. The expression levels of ATP‑binding cassette (ABC) transporter genes, including ABCC3, ABCC5 and ABCG2, were observed to be commonly repressed in EGFR‑TKI‑resistant cells. In addition, two cases were identified in which gemcitabine and vinorelbine exerted marked responses to lung cancers that had acquired resistance to EGFR‑TKIs, even with late‑line treatment. Therefore, it was proposed that gemcitabine and vinorelbine may be effective agents for patients with lung cancer previously treated with EGFR‑TKIs.

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