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

// Junjie Piao 1, 2, * , Liyan Chen 2, * , Taihao Quan 3 , Longshan Li 4 , Chunji Quan 1 , Yingshi Piao 1 , Tiefeng Jin 1, 2 , Zhenhua Lin 1 1 Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji 133002, China 2 Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules (Yanbian University), Ministry of Education, Yanji 133002, China 3 Department of Dermatology, University of Michigan Medical School, Michigan 48109-5609, USA 4 Department 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: jintf@ybu.edu.cn Zhenhua Lin, email: zhlin720@ybu.edu.cn 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.