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

18 Citations (Scopus)

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

Fingerprint

trichostatin A
Histone Deacetylase Inhibitors
Phosphatidylinositol 3-Kinases
Non-Small Cell Lung Carcinoma
Histone Deacetylases
Therapeutics
Epithelial-Mesenchymal Transition
dactolisib
Heterografts
Neoplasms
Proteins
Cell Proliferation
Apoptosis
Neoplasm Metastasis

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

Superior efficacy of co-treatment with the dual PI3K/mTOR inhibitor BEZ235 and histone deacetylase inhibitor Trichostatin A against NSCLC. / Piao, Junjie; Chen, Liyan; Quan, Taihao; Li, Longshan; Quan, Chunji; Piao, Yingshi; Jin, Tiefeng; Lin, Zhenhua.

In: Oncotarget, Vol. 7, No. 37, 2016, p. 60169-60180.

Research output: Contribution to journalArticle

Piao, Junjie ; Chen, Liyan ; Quan, Taihao ; Li, Longshan ; Quan, Chunji ; Piao, Yingshi ; Jin, Tiefeng ; Lin, Zhenhua. / Superior efficacy of co-treatment with the dual PI3K/mTOR inhibitor BEZ235 and histone deacetylase inhibitor Trichostatin A against NSCLC. In: Oncotarget. 2016 ; Vol. 7, No. 37. pp. 60169-60180.
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