N-terminal polypeptide derived from vMIP-II exerts its antitumor activity by inhibiting the CXCR4 pathway in human glioma
| Autor: | Sulian Chen, Lingyu Zhang, Jihong Zhou, Yingxiao Fu, Qingling Yang, Changjie Chen, Cong-Zhao Zhou, Lihua Zhu, Yu Li, Haihua Wu, Wenrui Wang, Haifeng Wang, Qiong Wu |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Stromal cell Cell Biology N-terminus peptide (NT21MP) Flow cytometry viral macrophage inflammatory protein II 03 medical and health sciences 0302 clinical medicine Cyclin D1 Glioma medicine MTT assay U251 CXCR4 brain gliomas medicine.diagnostic_test Articles Cell cycle medicine.disease 030104 developmental biology medicine.anatomical_structure Oncology Apoptosis 030220 oncology & carcinogenesis SHG-44 Cancer research |
| Zdroj: | International Journal of Oncology |
| ISSN: | 1791-2423 1019-6439 |
| Popis: | Emerging evidence demonstrates that the stromal derived factor-1 (SDF-1α)/CXCR4 axis is associated with tumor aggressiveness and metastasis, including glioma, the most common brain cancer. In the present study, we demonstrated that a novel designed peptide NT21MP of viral macrophage inflammatory protein II, targeting CXCR4 inhibits SDF-1α-induced activation in glioma. The effects of NT21MP on CXCR4 expression, cell survival and migration were assessed on the human glioma cell line U251 and SHG-44 exposed to SDF-1α, by western blotting, MTT assay, flow cytometry and transwell migration assay. Our results illustrated that NT21MP inhibited SDF-1α induced proliferation, migration and invasion by upregulated pro-apoptotic genes (Bak1 and caspase-3) and downregulated Bcl-2/Bax as well as cell cycle regulators (cyclin D1 and CDK4) to arrest cell cycle in G0/G1 phase and promote apoptosis. By RT-qPCR and immunofluorescence we found that CXCR4 was highly expressed in SHG-44 cells. Our results from wound healing and transwell invasion assays indicated silencing of CXCR4 significantly inhibited the SDF-1α‑induced migration and invasion; similarly, flow cytometry showed that treatment with si-CXCR4 affected cell cycle and induced cell apoptosis in SHG-44. However, these effects were significantly weakened by NT21MP. In conclusion, the present study indicates that NT21MP plays a regulatory role in the SDF-1α/CXCR4 axis and further manages the invasion, migration, apoptosis and cell cycle of glioma cells. Thus, NT21MP might represent a novel therapeutic approach against glioma. |
| Databáze: | OpenAIRE |
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