科研之友
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摘要
Emerging evidence demonstrates that the stromal derived factor-1 (SDF-1 alpha)/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-l alpha-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-l alpha, by western blotting, MTT assay, flow cytometry and Transwell migration assay. Our results illustrated that NT21MP inhibited SDF-l alpha induced proliferation, migration and invasion by upregulated pro-apoptotic genes (Bakl and caspase-3) and downregulated Bcl-2/Bax as well as cell cycle regulators (cyclin Dl 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-l alpha-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-l alpha/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.
