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BioMed Research International
Volume 2015, Article ID 642041, 11 pages
Research Article

Potential Therapeutic Benefit of Combining Gefitinib and Tamoxifen for Treating Advanced Lung Adenocarcinoma

1Sex Hormone Research Center, Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, 6 Xueshi Rd., North District, Taichung 40403, Taiwan
2Department of Chest Medicine, Taichung Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
3Department of Pathology, Taichung Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
4Center of Molecular Medicine, China Medical University Hospital, Taichung, Taiwan
5Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan

Received 29 August 2014; Revised 25 December 2014; Accepted 25 December 2014

Academic Editor: Noriyoshi Sawabata

Copyright © 2015 Chien-Ming Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Introduction. Epidermal growth factor receptor (EGFR) mutations are known as oncogene driver mutations and with EGFR mutations exhibit good response to the EGFR tyrosine kinase inhibitor Gefitinib. Some studies have shown that activation of estrogen and estrogen receptor α or β (ERα/β) promote adenocarcinoma. We evaluated the relationship between the two receptors and the potential therapeutic benefit with Gefitinib and Tamoxifen. Methods. We assessed the association between EGFR mutations as well as ERα/β expression/location and overall survival in a cohort of 55 patients with LAC from a single hospital. PC9 (EGFR exon 19 deletion mutant; Gefitinib-vulnerable cells) and A549 (EGFR wild type; Gefitinib-resistant cells) cancer cells were used to evaluate the in vitro therapeutic benefits of combining Gefitinib and Tamoxifen. Results. We found that the cytosolic but not the nuclear expression of ERβ was associated with better OS in LAC tumors but not associated with EGFR mutation. The in vitro study showed that combined Gefitinib and Tamoxifen resulted in increased apoptosis and cytosolic expression of ERβ. In addition, combining both medications resulted in reduced cell growth and increased the cytotoxic effect of Gefitinib. Conclusion. Tamoxifen enhanced advanced LAC cytotoxic effect induced by Gefitinib by arresting ERβ in cytosol.