title: Superior efficacy of co-treatment with the dual PI3K/mTOR inhibitor BEZ235 and histone deacetylase inhibitor Trichostatin A against NSCLC.
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.
authors: Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji 133002, China.|Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules (Yanbian University), Ministry of Education, Yanji 133002, China.
authors: Junjie
authors: J
authors: Piao
authors: Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules (Yanbian University), Ministry of Education, Yanji 133002, China.
authors: Liyan
authors: L
authors: Chen
authors: Department of Dermatology, University of Michigan Medical School, Michigan 48109-5609, USA.
authors: Taihao
authors: T
authors: Quan
authors: Department of Radiation Oncology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8807, USA.
authors: Longshan
authors: L
authors: Li
authors: Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji 133002, China.
authors: Chunji
authors: C
authors: Quan
authors: Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji 133002, China.
authors: Yingshi
authors: Y
authors: Piao
authors: Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji 133002, China.|Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules (Yanbian University), Ministry of Education, Yanji 133002, China.
authors: Tiefeng
authors: T
authors: Jin
authors: Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji 133002, China.
authors: Zhenhua
authors: Z
authors: Lin
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007093:Imidazoles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011804:Quinolines; D058570:TOR Serine-Threonine Kinases; C012589:trichostatin A; C546842:MTOR protein, human; C531198:dactolisib
keywords: BEZ235; TSA; epithelial-mesenchymal transition; non-small-cell lung cancer