Effects of anlotinib on the malignant phenotype of glioma cells by mediating NF-κB signaling pathway
OBJECTIVE To investigate the effects of anlotinib on the malignant phenotype of glioma cells by regulating the nuclear factor-κB(NF-κB)signaling pathway.METHODS Human glioma T98G cells were cultured in vitro,and 5-fluorouracil was used as positive control to investigate the effects of different concentrations of anlotinib(5,10,20 μmol/L)on the ability of proliferation,adhesion,migration and invasion,the expressions of epithelial-mesenchymal transition(EMT)related proteins[E-cadherin,N-cadherin,vimentin and fibronectin(FN)].NF-κB signaling pathway inhibitor(BAY 11-7082)and activator(prostratin)were additionally used to verify the possible mechanism of the above effects of anlotinib.RESULTS Anlotinib with 5,10,20 μmol/L could significantly decrease the activity of cell proliferation(except for 5 μmol/L anlotinib group),migration rate,and the number of adherent cells and invasive cells,could significantly up-regulate the expression of E-cadherin protein while down-regulate the expressions of N-cadherin,vimentin and FN protein(P<0.05);the effect of 20 μmol/L anlotinib was similar to that of positive control(P>0.05).Compared with 10 μmol/L anlotinib,pathway inhibitor could significantly decrease the ability of proliferation,adhesion,migration and invasion,and the expressions of N-cadherin,vimentin,FN and phosphorylated NF-κB p65 protein,while could significantly up-regulate the expression of E-cadherin protein(P<0.05);above indexes were reversed significantly by pathway activator(P<0.05).CONCLUSIONS Anlotinib may inhibit the proliferation,adhesion,migration and invasion of human glioma T98G cells,which may be associated with the inhibition of the NF-κB signaling pathway,thus inhibiting cell EMT-like processes.