Wnt/β-catenin pathway involvement in ionizing radiation-induced invasion of U87 glioblastoma cells

作者: Zhen Dong , Lin Zhou , Na Han , Mengxian Zhang , Xiaojuan Lyu

DOI: 10.1007/S00066-015-0858-7

关键词:

摘要: Radiotherapy has been reported to promote the invasion of glioblastoma cells; however, underlying mechanisms remain unclear. Here, we investigated role Wnt/β-catenin pathway in radiation-induced cells. U87 cells were irradiated with 3 Gy or sham presence absence inhibitor XAV 939. Cell was determined by an xCELLigence real-time cell analyser and matrigel assays. The intracellular distribution β-catenin without irradiation examined immunofluorescence Western blotting nuclear fractions. We next effect on activity using TOP/FOP flash luciferase assays quantitative polymerase chain reaction analysis target genes. expression levels activities two genes, matrix metalloproteinase (MMP)-2 MMP-9, further zymography. invasiveness increased significantly ionizing radiation. Interestingly, radiation induced translocation accumulation β-catenin. Moreover, found β-catenin/TCF transcriptional activities, followed up-regulation downstream genes Importantly, inhibition 939, which promotes degradation β-catenin, abrogated pro-invasion effects irradiation. Mechanistically, 939 suppressed radiation-triggered MMP-2 inhibited these gelatinases. Our data demonstrate a pivotal cells, suggest that targeting is promising therapeutic approach overcoming glioma radioresistance.

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