Potential Therapeutic Benefit of Combining Gefitinib and Tamoxifen for Treating Advanced Lung Adenocarcinoma
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 adeno...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2015-01-01
|
Series: | BioMed Research International |
Online Access: | http://dx.doi.org/10.1155/2015/642041 |
id |
doaj-16d73a1698e64a7bbc66bb29a29303d1 |
---|---|
record_format |
Article |
spelling |
doaj-16d73a1698e64a7bbc66bb29a29303d12020-11-24T21:16:22ZengHindawi LimitedBioMed Research International2314-61332314-61412015-01-01201510.1155/2015/642041642041Potential Therapeutic Benefit of Combining Gefitinib and Tamoxifen for Treating Advanced Lung AdenocarcinomaChien-Ming Liu0Kuo-Liang Chiu1Tzu-Sheng Chen2Shang-Miao Chang3Shu-Yun Yang4Li-Hsiou Chen5Yung-Lun Ni6Yuh-Pyng Sher7Sung-Liang Yu8Wen-Lung Ma9Sex Hormone Research Center, Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, 6 Xueshi Rd., North District, Taichung 40403, TaiwanDepartment of Chest Medicine, Taichung Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, Chiayi, TaiwanDepartment of Pathology, Taichung Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, Chiayi, TaiwanDepartment of Chest Medicine, Taichung Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, Chiayi, TaiwanSex Hormone Research Center, Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, 6 Xueshi Rd., North District, Taichung 40403, TaiwanDepartment of Chest Medicine, Taichung Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, Chiayi, TaiwanDepartment of Chest Medicine, Taichung Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, Chiayi, TaiwanCenter of Molecular Medicine, China Medical University Hospital, Taichung, TaiwanDepartment of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, TaiwanSex Hormone Research Center, Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, 6 Xueshi Rd., North District, Taichung 40403, TaiwanIntroduction. 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.http://dx.doi.org/10.1155/2015/642041 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chien-Ming Liu Kuo-Liang Chiu Tzu-Sheng Chen Shang-Miao Chang Shu-Yun Yang Li-Hsiou Chen Yung-Lun Ni Yuh-Pyng Sher Sung-Liang Yu Wen-Lung Ma |
spellingShingle |
Chien-Ming Liu Kuo-Liang Chiu Tzu-Sheng Chen Shang-Miao Chang Shu-Yun Yang Li-Hsiou Chen Yung-Lun Ni Yuh-Pyng Sher Sung-Liang Yu Wen-Lung Ma Potential Therapeutic Benefit of Combining Gefitinib and Tamoxifen for Treating Advanced Lung Adenocarcinoma BioMed Research International |
author_facet |
Chien-Ming Liu Kuo-Liang Chiu Tzu-Sheng Chen Shang-Miao Chang Shu-Yun Yang Li-Hsiou Chen Yung-Lun Ni Yuh-Pyng Sher Sung-Liang Yu Wen-Lung Ma |
author_sort |
Chien-Ming Liu |
title |
Potential Therapeutic Benefit of Combining Gefitinib and Tamoxifen for Treating Advanced Lung Adenocarcinoma |
title_short |
Potential Therapeutic Benefit of Combining Gefitinib and Tamoxifen for Treating Advanced Lung Adenocarcinoma |
title_full |
Potential Therapeutic Benefit of Combining Gefitinib and Tamoxifen for Treating Advanced Lung Adenocarcinoma |
title_fullStr |
Potential Therapeutic Benefit of Combining Gefitinib and Tamoxifen for Treating Advanced Lung Adenocarcinoma |
title_full_unstemmed |
Potential Therapeutic Benefit of Combining Gefitinib and Tamoxifen for Treating Advanced Lung Adenocarcinoma |
title_sort |
potential therapeutic benefit of combining gefitinib and tamoxifen for treating advanced lung adenocarcinoma |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2015-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2015/642041 |
work_keys_str_mv |
AT chienmingliu potentialtherapeuticbenefitofcombininggefitinibandtamoxifenfortreatingadvancedlungadenocarcinoma AT kuoliangchiu potentialtherapeuticbenefitofcombininggefitinibandtamoxifenfortreatingadvancedlungadenocarcinoma AT tzushengchen potentialtherapeuticbenefitofcombininggefitinibandtamoxifenfortreatingadvancedlungadenocarcinoma AT shangmiaochang potentialtherapeuticbenefitofcombininggefitinibandtamoxifenfortreatingadvancedlungadenocarcinoma AT shuyunyang potentialtherapeuticbenefitofcombininggefitinibandtamoxifenfortreatingadvancedlungadenocarcinoma AT lihsiouchen potentialtherapeuticbenefitofcombininggefitinibandtamoxifenfortreatingadvancedlungadenocarcinoma AT yunglunni potentialtherapeuticbenefitofcombininggefitinibandtamoxifenfortreatingadvancedlungadenocarcinoma AT yuhpyngsher potentialtherapeuticbenefitofcombininggefitinibandtamoxifenfortreatingadvancedlungadenocarcinoma AT sungliangyu potentialtherapeuticbenefitofcombininggefitinibandtamoxifenfortreatingadvancedlungadenocarcinoma AT wenlungma potentialtherapeuticbenefitofcombininggefitinibandtamoxifenfortreatingadvancedlungadenocarcinoma |
_version_ |
1726015841071267840 |