Oncotarget

Research Papers:

Superior efficacy of co-treatment with the dual PI3K/mTOR inhibitor BEZ235 and histone deacetylase inhibitor Trichostatin A against NSCLC

Junjie Piao, Liyan Chen, Taihao Quan, Longshan Li, Chunji Quan, Yingshi Piao, Tiefeng Jin _ and Zhenhua Lin

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Oncotarget. 2016; 7:60169-60180. https://doi.org/10.18632/oncotarget.11109

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Abstract

Junjie Piao1,2,*, Liyan Chen2,*, Taihao Quan3, Longshan Li4, Chunji Quan1, Yingshi Piao1, Tiefeng Jin1,2, Zhenhua Lin1

1Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji 133002, China

2Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules (Yanbian University), Ministry of Education, Yanji 133002, China

3Department of Dermatology, University of Michigan Medical School, Michigan 48109-5609, USA

4Department of Radiation Oncology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8807, USA

*These authors have contributed equally to this work

Correspondence to:

Tiefeng Jin, email: [email protected]

Zhenhua Lin, email: [email protected]

Keywords: non-small-cell lung cancer, TSA, BEZ235, epithelial-mesenchymal transition

Received: April 07, 2016    Accepted: July 19, 2016    Published: August 06, 2016

ABSTRACT

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. NSCLC development and progression have recently been correlated with the heightened activation of histone deacetylases (HDACs) and PI3K/Akt signaling pathways. Targeted inhibition of these proteins is promising approach for the development of novel therapeutic strategies to treat patients with advanced NSCLC. For this reason, we combined a dual PI3K and mTOR inhibitor, BEZ235 with the HDAC inhibitor Trichostatin A (TSA), to determine their combined effects on human NSCLC. In this study, we initially discovered that co-treatment with BEZ235 and TSA showed a synergistic effect on inhibition of NSCLC cell proliferation and induction of apoptosis. The combination treatment also synergistically suppressed NSCLC migration, invasion and the NSCLC epithelial-mesenchymal transition (EMT) in vitro. The synergistic effect was also evidenced by declines in xenograft growth and metastasis rates and in ki-67 protein expression in vivo. Together, these results indicated that BEZ235 and TSA combination treatment significantly increased anti-tumor activities compared with BEZ235 and TSA alone, supporting a further evaluation of combination treatment for NSCLC.


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