A novel approach to eliminate therapy-resistant mantle cell lymphoma: synergistic effects of Vorinostat with Palbociclib
| Autor: | Matthew J. Kling, Nagendra K. Chaturvedi, Garrett L. Sutton, Shantaram S. Joshi, Julie M. Vose, Nathan D. Hatch |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Cancer Research
Pyridines Apoptosis Lymphoma Mantle-Cell Palbociclib Piperazines 03 medical and health sciences 0302 clinical medicine immune system diseases hemic and lymphatic diseases Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Humans neoplasms Vorinostat Cell Proliferation Cell growth Chemistry Cell Cycle Drug Synergism Hematology Cell cycle medicine.disease Lymphoma Oncology Cell culture Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research Mantle cell lymphoma 030215 immunology medicine.drug |
| Zdroj: | Leukemialymphoma. 60(5) |
| ISSN: | 1029-2403 |
| Popis: | Mantle cell lymphoma (MCL) represents an aggressive B-cell lymphoma with frequent relapse and poor survival. Recently, dysregulated histone-deacetylases (HDACs) and cell cycle CDK-Rb pathway have been shown to be commonly associated with MCL pathogenesis, and are considered promising targets for relapsed-lymphoma therapy. Therefore, we investigated the single agents and combination efficacy of HDACs inhibitor Vorinostat, CDK4/6 dual-inhibitor Palbociclib on MCL cell growth/survival and underlying molecular mechanism(s) using MCL cell lines including therapy-resistant MCL cell lines. Our results showed that both inhibitors as single agents or combined, significantly suppressed the cell growth and induced apoptosis in therapy-resistant and parental MCL lines. In addition, the combination of Vorinostat and Palbociclib significantly inhibited the activation of the key molecules of the CDK4/6-Rb pathway and HDAC activity and subsequently decreased the expression of Cyclin-D1 and Bcl-2. These studies demonstrated the potential for combining these two inhibitors as a novel therapeutic approach in refractory MCL therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|