The combination of BET and HDAC inhibition as a therapeutic approach in sensitizing drug-resistant meningioma cells to chemotherapy

Date

2023-8-15

Author

Neyişci, Özlem

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

293
views

276
downloads

Cite This

Cancer and drug resistance still pose significant challenges in modern oncology. Meningioma, a prevalent type of central nervous system tumor, frequently exhibits resistance to conventional chemotherapy. This study aims to investigate the potential of epigenomic drug interventions as either single or dual combinations in overcoming JQ1 (a BRD4 inhibitor) chemoresistance in meningioma. SAHA (suberoylanilide hydroxamic acid, an HDAC inhibitor) and JQ1 were utilized individually and in combination to assess whether SAHA could sensitize chemoresistant meningioma progression in the benign BenMen 599 and malignant CH157 MN meningioma cell lines, including their resistant counterparts. The impact of single or combined drugs on cell viability and toxicity, cell cycle distribution, and gene expression changes was examined and compared among the different treatment approaches. Overall, the present study offers scientific support for the efficacy of combined HDAC and BRD4 inhibition by using SAHA and JQ1 drugs respectively to sensitize chemoresistant meningioma cells, specifically in the CH157MN meningioma cell line. Our current findings strongly suggest that the synergistic effects on cell survival and cell cycle distribution as well as the downregulation of apoptosis inhibitors emphasize the possibility of combination therapy as a promising technique for improving chemoresistant meningioma treatment results. The proposed combined HDAC and BRD4 inhibition can be checked for the treatment of other cancer cells which have similar regulation of epigenome for chemoresistance with CH157MN meningioma cells. So that this promising combination therapy can be used not only in malignant meningiomas but also in other cancer types with similar epigenetic regulation.

Subject Keywords

Meningioma, Drug Resistance, Combinatorial Therapies

URI

https://hdl.handle.net/11511/104895

Collections

Graduate School of Natural and Applied Sciences, Thesis