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, Zhenhua Lin

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)60169-60180
Number of pages12
JournalOncotarget
Volume7
Issue number37
DOIs
StatePublished - 2016

Keywords

  • BEZ235
  • Epithelial-mesenchymal transition
  • Non-small-cell lung cancer
  • TSA

ASJC Scopus subject areas

  • Oncology

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