HDAC6 promotes cell proliferation and confers resistance to gefitinib in lung adenocarcinoma

Wang,Zhihao; Tang,Fang; Hu,Pengchao; Wang,Ying; Gong,Jun; Sun,Shaoxing; Xie,Conghua

doi:10.3892/or.2016.4811

HDAC6 promotes cell proliferation and confers resistance to gefitinib in lung adenocarcinoma

Authors:
- Zhihao Wang
- Fang Tang
- Pengchao Hu
- Ying Wang
- Jun Gong
- Shaoxing Sun
- Conghua Xie
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Affiliations: Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuchang, Wuhan 430071, P.R. China, Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuchang, Wuhan 430071, P.R. China
Published online on: May 16, 2016 https://doi.org/10.3892/or.2016.4811
Pages: 589-597

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Abstract

Histone deacetylases (HDACs) are promising targets for cancer therapy, and first-generation HDAC inhibitors are currently in clinical trials for the treatment of cancer patients. HDAC6, which is a key regulator of many signaling pathways that are linked to cancer, has recently emerged as an attractive target for the treatment of cancer. In the present study, HDAC6 was found to be overexpressed in lung adenocarcinoma cell lines and was negatively correlated with the prognosis of patients with lung adenocarcinoma. Overexpression of HDAC6 promoted the proliferation of lung adenocarcinoma cells in a deacetylase activity-dependent manner. HDAC6 overexpression conferred resistance to gefitinib via the stabilization of epidermal growth factor receptor (EGFR). The inhibition of HDAC6 by CAY10603, a potent and selective inhibitor of HDAC6, inhibited the proliferation of lung adenocarcinoma cells and induced apoptosis. CAY10603 downregulated the levels of EGFR protein, which in turn inhibited activation of the EGFR signaling pathway. Moreover, CAY10603 synergized with gefitinib to induce apoptosis of the lung adenocarcinoma cell lines via the destabilization of EGFR. Taken together, our results suggest that the inhibition of HDAC6 may be a promising strategy for the treatment of lung adenocarcinoma.

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