AZD3759 inhibits glioma through the blockade of the epidermal growth factor receptor and Janus kinase pathways
| Autor: | Qinghua Deng, Qingqing Yu, Wei Yin, Ruping Zhao, Ke Zhang, Yanjiao Mao, Shenglin Ma |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Bioengineering Apoptosis Applied Microbiology and Biotechnology Piperazines Mice Glioma glioma medicine Tumor Cells Cultured Animals Humans Osimertinib Epidermal growth factor receptor EGFR inhibitors Cell Proliferation Janus Kinases biology Chemistry Brain Neoplasms JAK-STAT signaling pathway janus kinase General Medicine Cell cycle medicine.disease Xenograft Model Antitumor Assays ErbB Receptors Gene Expression Regulation Neoplastic osimertinib Cancer research biology.protein Quinazolines Janus kinase azd3759 epidermal growth factor receptor TP248.13-248.65 Research Article Research Paper Biotechnology |
| Zdroj: | Bioengineered, Vol 12, Iss 1, Pp 8679-8689 (2021) Bioengineered article-version (VoR) Version of Record |
| ISSN: | 2165-5987 2165-5979 |
| Popis: | Glioma is an intracranial malignant tumor with high morbidity in China. Limited efficacy has been achieved in the treatment of glioma through the application of epidermal growth factor receptor (EGFR) inhibitors, which is reported to be related to the poor permeability of the brain–blood barrier (BBB) to EGFR inhibitors. AZD3759 and osimertinib are both BBB-penetrating EGFR inhibitors. The present study aimed to investigate the inhibitory effects of AZD3759 and osimertinib on glioma and compare their efficacy and the underlying mechanisms. C6 and U87 cells were incubated with different concentrations of AZD3759 (1, 2, and 4 μM) and 4 μM osimertinib, respectively. C6-LUC xenograft animals were administered different doses of AZD3759 (15, 30, and 60 mg/kg) and 60 mg/kg osimertinib. We found that proliferation was significantly suppressed and that apoptosis and cell cycle arrest were dramatically induced in both C6 and U87 cells by AZD3759 in a dose-dependent manner. Compared to AZD3759, osimertinib had inferior effects on proliferation, apoptosis, and cell cycle. In vivo experiments verified that the anti-tumor efficacy of AZD3759 against C6 xenograft tumors was dose dependent and superior to that of osimertinib. The inhibitory effects of AZD3759 on the Janus kinase (JAK)/STAT pathway were observed in both glioma cells and tumor tissues, which were more significant than those of osimertinib. In conclusion, AZD3759 may inhibit the progression of glioma via a synergistic blockade of the EGFR and JAK/STAT signaling pathways. |
| Databáze: | OpenAIRE |
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