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Over-Expression of Beclin-1 Facilitates Acquired Resistance to Histone Deacetylase Inhibitor-Induced Apoptosis

  • Wang, Shi-Miao (School of Life Science and Biotechnology, Dalian University of Technology) ;
  • Li, Xiao-Hui (School of Life Science and Biotechnology, Dalian University of Technology) ;
  • Xiu, Zhi-Long (School of Life Science and Biotechnology, Dalian University of Technology)
  • Published : 2014.10.11

Abstract

Apoptotic cell death plays a predominant role in histone deacetylase (HDAC) inhibitor-induced cytotoxicity. Nuclear morphological changes and activation of apoptotic executors are involved in CTS203-induced cell death. However, emerging issues of HDAC inhibitor-resistance have been observed in patients. Herein, MCF-7 cells were continuously exposed to CTS203 until the derived cells could proliferate normally in its presence. The newly obtained CTS203-resistant cells were nominated as MCF-7/203R. Compared to MCF-7 original cells, the MCF-7/203R cells were less sensitive to CTS203-induced apoptosis, with a minimal 6-fold higher $IC_{50}$ value. In contrast, the expression of Beclin-1 was dramatically up-regulated, positively correlated to the acquisition of CTS203-resistance. Our results revealed the participation of autophagy in acquired HDAC inhibitor-resistance and further identified Beclin-1 as a promising target for anti-drug resistance.

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