| Autor: |
Teng Li, Xuhui Yuan, Feifei Zhang, Jiayu Li, Qi Liao, Xiao-Bin Lv, Yuanxiang Peng, Feng Cai, Bo Yu, Yiping Liang, Zhengzai Dai, Xiaofeng Tang, Duo Zeng, Liu Lang |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.21203/rs.3.rs-594853/v1 |
| Popis: |
Background: Osteosarcoma (OS) is a tumor with a high malignancy level and a poor prognosis. First-line chemotherapy for OS has not been improved for many decades. Bromodomain and extra terminal domain (BET) and histone deacetylase (HDACs) regulate histone acetylation in tandem, and BET and HDACs have emerged as potential cancer therapeutic targets. Methods: Cell proliferation, migration, invasion, colony formation, and sphere-forming assay were performed with the two inhibitors alone or in combination to evaluate their suppressing effect on malignant properties of OS cells. The apoptosis and cells-cycle profile were measured by flow cytometry. The synergistic inhibitory effect of OTX015/WT-161 on tumor was also examined in a nude mouse xenograft model. Results: The combined therapy of OTX015/WT-161 synergistically inhibited the growth, migration, and invasion and induced apoptosis, resulted in the G1/S arrest of OS cells. Additionally, OTX015/WT-161 inhibits the self-renewal ability of OS stem cells (OSCs) in a synergistic manner. Further mechanistic exploration uncovered that the synergistic downregulation of β-catenin by OTX015-mediated suppression of FZD2 and WT-161-mediated upregulation of PTEN may be responsible for the synergistic effect. Finally, the result of an in vivo assay showed that tumor xenografts were significantly decreased after treatment with OTX015/WT-161 combination compared with OTX015 or WT-161 alone. Conclusion: Our findings in this study demonstrated that OTX015 and WT-161 had a synergistic anti-cancer efficacy against OS, and their combination might be a promising therapeutic strategy for OS. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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