Effect of nabrphine on proliferation,migration,and invasion of glioma cells by regulating the hypoxia inducible factor-1 α/vascularendothelial growth factor signaling pathway
Objective To investigate the effects of nalbuphine(NAL)on the proliferation,migra-tion,and invasion of glioma cells,and its regulatory mechanism on hypoxia inducible factor-1α(HIF-1α)/vascularendothelial growth factor(VEGF)signaling pathway.Methods Human glioma cells U251 were cultured and randomly separated into U251 group,NAL low concentration(NAL-L)group,NAL medium concentration(NAL-M)group,NAL high concentration(NAL-H)group,and NAL-H+HIF-1α activator(NAL-H+DMOG)group.The CCK-8 method was applied to detect the survival rate of U251 cells in each group.Cloning plate experiment was applied to detect the cloning ability of U251 cells in each group.Transwell experiment was applied to detect the number of migrating and invasive U251 cells in each group.Western blotting was applied to detect the HIF-1α/VEGF signaling pathway and the relative expression lev-els of epithelial mesenchymal transition related proteins(E-cadherin,Vimentin,and N-cadherin)in each group.All data were analyzed using GraphPad Prism 9.0 software,and one-way ANOVA was used to com-pare the differences in multiple indicators between groups.Tukey's post hoc test was used for multiple comparison analysis between two groups.Results The cell survival rates in NAL-L group,NAL-M group and NAL-H group[(62.33±4.51)％,(41.06±3.37)％,(31.32±2.09)％],number of clones formed[(162.38±4.97),(146.03±3.66),(127.59±2.96)],number of migrating and invading cells[(106.33±2.57,69.60±2.44),(92.37±2.09,54.70±2.03),(80.91±1.76,41.66±1.62)],and HIF-1α(0.78±0.07,0.61±1.62,0.48±0.04),VEGF(0.72±0.06,0.60±0.05,0.43±0.03),Vim-entin(0.80±0.07,0.68±0.05,0.47±0.03),the relative expression levels of N-cadherin(0.71±0.06,0.56±0.04,0.40±0.03)were lower than those in the U251 group(P＜0.05),while the expression levels of E-cadherin(1.21±0.09,1.47±0.13,1.67±0.17)were higher than those in the U251 group(P＜0.05).The addition of HIF-1α activator DMOG to U251 cells treated with high concentration of NAL reversed the trend of changes in the above indicators(P＜0.05).Conclusion NAL can inhibit HIF-1α/VEGF signaling pathway to inhibit the proliferation,migration,and invasion of glioma cells.
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