期刊
JOURNAL OF MOLECULAR NEUROSCIENCE
卷 68, 期 1, 页码 49-57出版社
HUMANA PRESS INC
DOI: 10.1007/s12031-019-01280-5
关键词
Brain tumor; Epidermal growth factor receptor; Chromatin; Glioblastoma; Growth factor receptor; Histone deacetylase
资金
- National Council for Scientific and Technological Development (CNPq) [303276/2013-4, 409287/2016-4]
- Coordination for the Improvement of Higher Education Personnel (CAPES)
- Children's Cancer Institute (ICI)
- Clinical Hospital institutional research fund (FIPE/HCPA)
Changes in expression of histone deacetylases (HDACs), which epigenetically regulate chromatin structure, and mutations and amplifications of the EGFR gene, which codes for the epidermal growth factor receptor (EGFR), have been reported in glioblastoma (GBM), the most common and malignant type of brain tumor. There are likely interplays between HDACs and EGFR in promoting GBM progression, and HDAC inhibition can cooperate with EGFR blockade in reducing the growth of lung cancer cells. Here, we found that either HDAC or EGFR inhibitors dose-dependently reduced the viability of U87 and A-172 human GBM cells. In U87 cells, the combined inhibition of HDACs and EGFR was more effective than inhibiting either target alone in reducing viability and long-term proliferation. In addition, HDAC or EGFR inhibition, alone or combined, led to G0/G1 cell cycle arrest. The EGFR inhibitor alone or combined with HDAC inhibition increased mRNA expression of the signal transducer and activator of transcription 3 (STAT3), which can act either as an oncogene or a tumor suppressor in GBM. These data provide early evidence that combining HDAC and EGFR inhibition may be an effective strategy to reduce GBM growth, through a mechanism possibly involving STAT3.
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