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Cancers 2019, 11(3), 282;

Nicotine Induces Resistance to Erlotinib Therapy in Non-Small-Cell Lung Cancer Cells Treated with Serum from Human Patients

Department of Pulmonary Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto 602-0841, Japan
Department of Internal Medicine, Self Defense Forces Fukuoka Hospital, Fukuoka 816-0826, Japan
Author to whom correspondence should be addressed.
Received: 20 February 2019 / Accepted: 25 February 2019 / Published: 27 February 2019
(This article belongs to the Special Issue Epidermal Growth Factor Receptor Signaling in Cancer)
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Previously, we reported that nicotine reduces erlotinib sensitivity in a xenograft model of PC9, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-sensitive non-small-cell lung cancer cell line. The present study examined whether smoking induces erlotinib resistance in vitro. We assessed resistance to EGFR-TKIs by treating cancer cell lines with erlotinib, afatinib, or osimertinib, and serum collected from smokers within 30 min of smoking and that from a non-smoker as a control. We also assessed erlotinib resistance by treating PC9 cells exposed to serum from a smoker or a non-smoker, or serum from an erlotinib user. Treatment of the cancer cell lines with serum from smokers induced significant erlotinib resistance, compared with the control (p < 0.05). Furthermore, serum samples with a high concentration of cotinine (a nicotine exposure indicator) demonstrated stronger erlotinib resistance than those with low concentrations. Similar to the observations with erlotinib treatment of cell lines, the analysis of serum from erlotinib users revealed that smokers demonstrated significantly reduced sensitivity to erlotinib (p < 0.001). In conclusion, our present results support the hypothesis that smoking contributes to resistance to erlotinib therapy in non-small-cell lung cancer. View Full-Text
Keywords: cotinine; nicotine; non-small-cell lung cancer (NSCLC); EGFR; erlotinib resistance cotinine; nicotine; non-small-cell lung cancer (NSCLC); EGFR; erlotinib resistance

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Imabayashi, T.; Uchino, J.; Osoreda, H.; Tanimura, K.; Chihara, Y.; Tamiya, N.; Kaneko, Y.; Yamada, T.; Takayama, K. Nicotine Induces Resistance to Erlotinib Therapy in Non-Small-Cell Lung Cancer Cells Treated with Serum from Human Patients. Cancers 2019, 11, 282.

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