Enhanced efficacy of histone deacetylase inhibitor combined with bromodomain inhibitor in glioblastoma
Abstract Background Glioblastoma (GBM) is the most common and most malignant primary brain cancer in adults. Despite multimodality treatment, the prognosis is still poor. Therefore, further work is urgently required to discover novel therapeutic strategies for GBM treatment. Methods The synergistic...
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| Format: | Article |
| Language: | English |
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BMC
2018-10-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | http://link.springer.com/article/10.1186/s13046-018-0916-y |
| _version_ | 1818317126907199488 |
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| author | Wei Meng Baocheng Wang Weiwei Mao Jiajia Wang Yang Zhao Qifeng Li Chenran Zhang Yujie Tang Jie Ma |
| author_facet | Wei Meng Baocheng Wang Weiwei Mao Jiajia Wang Yang Zhao Qifeng Li Chenran Zhang Yujie Tang Jie Ma |
| author_sort | Wei Meng |
| collection | DOAJ |
| description | Abstract Background Glioblastoma (GBM) is the most common and most malignant primary brain cancer in adults. Despite multimodality treatment, the prognosis is still poor. Therefore, further work is urgently required to discover novel therapeutic strategies for GBM treatment. Methods The synergistic effects of cotreatment with the histone deacetylase (HDAC) inhibitor panobinostat and bromodomain inhibitor JQ1 or OTX015 were validated using cell viability assays in GBM cell lines. Furthermore, the inhibitory mechanisms were investigated via an EdU proliferation assay, an apoptosis assay, qPCR, Western blot and RNAseq analyses. Results We found that the cotreatment with panobinostat and JQ1 or OTX015 synergistically inhibited cell viability in GBM cells. The cotreatment with panobinostat and JQ1 or OTX015 markedly inhibited cell proliferation and induced apoptosis in GBM cells. Compared with treatment with each drug alone, the cotreatment with panobinostat and JQ1 induced more profound caspase 3/7 activation and cytotoxicity. Mechanistic investigation showed that combination of panobinostat with JQ1 or OTX015 results in stronger repression of GBM-associated oncogenic genes or pathways as well as higher induction of GBM-associated tumor-suppressive genes. Conclusion Our study demonstrated that HDAC inhibitor and bromodomain inhibitor had synergistical efficacy against GBM cells. The cotreatment with HDAC inhibitor and bromodomain inhibitor warrants further attention in GBM therapy. |
| first_indexed | 2024-12-13T09:32:22Z |
| format | Article |
| id | doaj.art-1dee1e549d2d4486b271bfdf34617805 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-13T09:32:22Z |
| publishDate | 2018-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-1dee1e549d2d4486b271bfdf346178052022-12-21T23:52:28ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662018-10-0137111110.1186/s13046-018-0916-yEnhanced efficacy of histone deacetylase inhibitor combined with bromodomain inhibitor in glioblastomaWei Meng0Baocheng Wang1Weiwei Mao2Jiajia Wang3Yang Zhao4Qifeng Li5Chenran Zhang6Yujie Tang7Jie Ma8Department of Pediatric Neurosurgery, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Neurosurgery, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Neurosurgery, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Neurosurgery, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Neurosurgery, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Neurosurgery, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Neurosurgery, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Neurosurgery, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Neurosurgery, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University School of MedicineAbstract Background Glioblastoma (GBM) is the most common and most malignant primary brain cancer in adults. Despite multimodality treatment, the prognosis is still poor. Therefore, further work is urgently required to discover novel therapeutic strategies for GBM treatment. Methods The synergistic effects of cotreatment with the histone deacetylase (HDAC) inhibitor panobinostat and bromodomain inhibitor JQ1 or OTX015 were validated using cell viability assays in GBM cell lines. Furthermore, the inhibitory mechanisms were investigated via an EdU proliferation assay, an apoptosis assay, qPCR, Western blot and RNAseq analyses. Results We found that the cotreatment with panobinostat and JQ1 or OTX015 synergistically inhibited cell viability in GBM cells. The cotreatment with panobinostat and JQ1 or OTX015 markedly inhibited cell proliferation and induced apoptosis in GBM cells. Compared with treatment with each drug alone, the cotreatment with panobinostat and JQ1 induced more profound caspase 3/7 activation and cytotoxicity. Mechanistic investigation showed that combination of panobinostat with JQ1 or OTX015 results in stronger repression of GBM-associated oncogenic genes or pathways as well as higher induction of GBM-associated tumor-suppressive genes. Conclusion Our study demonstrated that HDAC inhibitor and bromodomain inhibitor had synergistical efficacy against GBM cells. The cotreatment with HDAC inhibitor and bromodomain inhibitor warrants further attention in GBM therapy.http://link.springer.com/article/10.1186/s13046-018-0916-yGlioblastomaPanobinostatJQ1OTX015 |
| spellingShingle | Wei Meng Baocheng Wang Weiwei Mao Jiajia Wang Yang Zhao Qifeng Li Chenran Zhang Yujie Tang Jie Ma Enhanced efficacy of histone deacetylase inhibitor combined with bromodomain inhibitor in glioblastoma Journal of Experimental & Clinical Cancer Research Glioblastoma Panobinostat JQ1 OTX015 |
| title | Enhanced efficacy of histone deacetylase inhibitor combined with bromodomain inhibitor in glioblastoma |
| title_full | Enhanced efficacy of histone deacetylase inhibitor combined with bromodomain inhibitor in glioblastoma |
| title_fullStr | Enhanced efficacy of histone deacetylase inhibitor combined with bromodomain inhibitor in glioblastoma |
| title_full_unstemmed | Enhanced efficacy of histone deacetylase inhibitor combined with bromodomain inhibitor in glioblastoma |
| title_short | Enhanced efficacy of histone deacetylase inhibitor combined with bromodomain inhibitor in glioblastoma |
| title_sort | enhanced efficacy of histone deacetylase inhibitor combined with bromodomain inhibitor in glioblastoma |
| topic | Glioblastoma Panobinostat JQ1 OTX015 |
| url | http://link.springer.com/article/10.1186/s13046-018-0916-y |
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