2. Academic Validation
  3. HDAC6 promotes cell proliferation and confers resistance to temozolomide in glioblastoma

HDAC6 promotes cell proliferation and confers resistance to temozolomide in glioblastoma

  • Cancer Lett. 2016 Aug 28;379(1):134-42. doi: 10.1016/j.canlet.2016.06.001.
Zhihao Wang 1,  Pengchao Hu 2,  Fang Tang 3,  Haiwei Lian 4,  Xiong Chen 2,  Yingying Zhang 2,  Xiaohua He 2,  Wanhong Liu 5,  Conghua Xie 6
Affiliations

Affiliations

  • 1 Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China; School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
  • 2 School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
  • 3 Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 4 Department of Neurosurgery, Wuhan University Renmin Hospital, Wuhan 430060, China.
  • 5 School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. Electronic address: liuwanhong@whu.edu.cn.
  • 6 Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China. Electronic address: chxie_65@whu.edu.cn.
PMID: 27267806 DOI: 10.1016/j.canlet.2016.06.001
Abstract

Histone deacetylases are considered to be among the most promising targets in drug development for Cancer therapy. Histone deacetylase 6 (HDAC6) is a unique cytoplasmic Enzyme that regulates many biological processes involved in tumorigenesis through its deacetylase and ubiquitin-binding activities. Here, we report that HDAC6 is overexpressed in glioblastoma tissues and cell lines. Overexpression of HDAC6 promotes the proliferation and spheroid formation of glioblastoma cells. HDAC6 overexpression confers resistance to temozolomide (TMZ) mediated cell proliferation inhibition and Apoptosis induction. Conversely, knockdown of HDAC6 inhibits cell proliferation, impairs spheroid formation and sensitizes glioblastoma cells to TMZ. The inhibition of HDAC6 deacetylase activity by selective inhibitors inhibits the proliferation of glioblastoma cells and induces Apoptosis. HDAC6 selective inhibitors can sensitize glioblastoma cells to TMZ. Moreover, we showed that HDAC6 mediated EGFR stabilization might partly account for its oncogenic role in glioblastoma. TMZ resistant glioblastoma cells showed higher expression of HDAC6 and more activation of EGFR. HDAC6 inhibitors decrease EGFR protein levels and impair the activation of the EGFR pathway. Taken together, our results suggest that the inhibition of HDAC6 may be a promising strategy for the treatment of glioblastoma.

Keywords

EGFR; Glioblastoma; HDAC6; Temozolomide.

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