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Signal Transducer and Activator of Transcription 3 as Molecular Therapy for Non–Small-Cell Lung Cancer

Signal Transducer and Activator of Transcription 3 as Molecular Therapy for Non–Small-Cell... ORIGINAL ARTICLE Signal Transducer and Activator of Transcription 3 as  Molecular Therapy for Non–Small-Cell Lung Cancer Cheng-Yi Wang, MD,*†‡ Ting-Ting Chao, PhD,* Wei-Tien Tai, PhD,§ǁ Fang-Yu Chang, MS,* Wen-Pin Su, MD, PhD,¶ Yen-Lin Chen, MD,# Pao-Tzu Chen, BsC,* Ching-Yu Weng, BsC,* Ang Yuan, MD, PhD,** Chung-Wai Shiau, PhD,†† Chong-Jen Yu, MD, PhD,‡‡ and Kuen-Feng Chen, MD, PhD§ǁ apoptosis. SC-1 significantly reduced H460 and A549 tumor growth Introduction: Targeting signal transducer and activator of transcrip- in vivo through SHP-1/STAT3 pathway. tion 3 (STAT3), a transcription factor that modulates survival-directed Conclusions: SC-1 provides proof that targeting STAT3 signal- transcription, is often persistently activated in epidermal growth factor ing pathway may be a novel approach for the treatment of EGFR receptor (EGFR) wild-type non–small-cell lung cancer (NSCLC). The wild-type NSCLC. aim of this study was to determine whether sorafenib and its deriva- tive can inhibit EGFR wild-type NSCLC via STAT3 inactivation. Key Words: Sorafenib, Cyclin D1, Survivin, Non–small-cell lung Methods: EGFR wild-type NSCLC cell lines (A549 H292 H322 cancer, STAT3. H358 and H460) were treated with sorafenib or SC-1, a sorafenib (J Thorac Oncol. 2014;9: 488–496) derivative that closely resembled sorafenib structurally but was devoid of kinase inhibitory activity. Apoptosis and signal transduc- tion were analyzed. In vivo efficacy was determined in nude mice http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Thoracic Oncology Wolters Kluwer Health

Signal Transducer and Activator of Transcription 3 as Molecular Therapy for Non–Small-Cell Lung Cancer

Chen, Kuen-Feng
Journal of Thoracic Oncology , Volume 9 (4) – Apr 1, 2014
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Copyright
Copyright © 2014 by the International Association for the Study of Lung Cancer
ISSN
1556-0864
DOI
10.1097/JTO.0000000000000107
pmid
24736071
Publisher site
See Article on Publisher Site

Abstract

ORIGINAL ARTICLE Signal Transducer and Activator of Transcription 3 as  Molecular Therapy for Non–Small-Cell Lung Cancer Cheng-Yi Wang, MD,*†‡ Ting-Ting Chao, PhD,* Wei-Tien Tai, PhD,§ǁ Fang-Yu Chang, MS,* Wen-Pin Su, MD, PhD,¶ Yen-Lin Chen, MD,# Pao-Tzu Chen, BsC,* Ching-Yu Weng, BsC,* Ang Yuan, MD, PhD,** Chung-Wai Shiau, PhD,†† Chong-Jen Yu, MD, PhD,‡‡ and Kuen-Feng Chen, MD, PhD§ǁ apoptosis. SC-1 significantly reduced H460 and A549 tumor growth Introduction: Targeting signal transducer and activator of transcrip- in vivo through SHP-1/STAT3 pathway. tion 3 (STAT3), a transcription factor that modulates survival-directed Conclusions: SC-1 provides proof that targeting STAT3 signal- transcription, is often persistently activated in epidermal growth factor ing pathway may be a novel approach for the treatment of EGFR receptor (EGFR) wild-type non–small-cell lung cancer (NSCLC). The wild-type NSCLC. aim of this study was to determine whether sorafenib and its deriva- tive can inhibit EGFR wild-type NSCLC via STAT3 inactivation. Key Words: Sorafenib, Cyclin D1, Survivin, Non–small-cell lung Methods: EGFR wild-type NSCLC cell lines (A549 H292 H322 cancer, STAT3. H358 and H460) were treated with sorafenib or SC-1, a sorafenib (J Thorac Oncol. 2014;9: 488–496) derivative that closely resembled sorafenib structurally but was devoid of kinase inhibitory activity. Apoptosis and signal transduc- tion were analyzed. In vivo efficacy was determined in nude mice

Journal

Journal of Thoracic Oncology – Wolters Kluwer Health

Published: Apr 1, 2014

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