Oncotarget

Research Papers:

PI3K/mTOR dual inhibitor BEZ235 and histone deacetylase inhibitor Trichostatin A synergistically exert anti-tumor activity in breast cancer

Liyan Chen, Tiefeng Jin, Kun Zhu, Yingshi Piao, Taihao Quan, Chunji Quan and Zhenhua Lin _

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Oncotarget. 2017; 8:11937-11949. https://doi.org/10.18632/oncotarget.14442

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Abstract

Liyan Chen1,2,*, Tiefeng Jin1,*, Kun Zhu2, Yingshi Piao1, Taihao Quan3, Chunji Quan1, Zhenhua Lin1

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

2Department of Biochemistry and Molecular Biology, Yanbian University Medical College, Yanji 133002, China

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

*These authors have contributed equally to this work

Correspondence to:

Zhenhua Lin, email: [email protected]

Keywords: breast cancer, BEZ235, Trichostatin A, apoptosis, autophagy

Received: October 12, 2016    Accepted: December 27, 2016    Published: January 02, 2017

ABSTRACT

Molecule-targeted therapy has achieved great progress in cancer therapy. Effective drug combinations are one way to enhance the therapeutic efficacy and combat resistance. Here, we determined the effect of the PI3K/mTOR dual inhibitor BEZ235 and the histone deacetylase inhibitor Trichostatin A (TSA) on human breast cancer. We demonstrated that the combination of BEZ235 and TSA results in significant synergistic growth inhibition of multiple breast cancer cell lines. Mechanistic studies revealed that the combined therapy induced apoptosis in a caspase-dependent manner, which might be related to the further depression of the PI3K/Akt/mTOR signalling pathway. Additionally, co-treatment with BEZ235 and TSA enhanced autophagic cell death by up-regulating the expression of LC3B-II and Beclin-1. The vivo tumour modelling studies revealed that BEZ235 combined with TSA blocked tumour growth without noticeable side effects. These data suggest that the combination of BEZ235 and TSA may be a new selective strategy, which may have significant clinical application in the treatment of breast cancer patients.


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