Sodium Selenite Inhibits Glycolysis And Promotes Apoptosis Of Lung Cancer Cells Through The NFκB/PDK Axis

BackgroundLung cancer is the leading cause of cancer-related mortality worldwide.Sodium selenite(SSe)has an array of pharmacological and biochemical properties,including anti-neoplastic,anti-inflammatory and anti-inflammatory activity.However,the specific mechanisms underlying these properties are unknown.The aim of this study is to explore the anti-tumor mechanisms of SSe in lung cancer.Methods The viability of lung cancer cells treated with SSe was evaluated using CCK-8 assay.The ability of lung cancer cells to migrate was observed by cell scratch assay.The effect of SSe in promoting apoptosis of lung cancer cells was investigated by flow cytometry assay.JC-1 assay was used to analyze mitochondrial membrane potential in lung cancer cells treated with SSe.The expression of PDK,cytochrome c,Bcl-2 and Bax in A549 and PC9 cells treated with SSe was detected by q PCR.Western blotassay was used to detected the expression of p-p65,p65,p-IκBα,IκBα,PDK,Bcl-2,Bax and cytochrome c in A549 and PC9 cells treated with SSe,BAY11-7082 and the p65 plasmid overpression.The changed subcellular localization of p65 in lung cancer A549 and PC9 cells treated with SSe and BAY11-7082 was detected by immunofluorescence staining.Hematoxylin-eosin(HE)staining and immunohistochemical stainingwere used to detect the effect of SSe on the tumor growth of lung cancer cell xenograft mice model.The expression of p-p65,p65,p-IκBα,IκBα,PDK,Bcl-2,Bax and cytochrome c were detected by Western blot.Results The results of the CCK-8,cell scratch assay,Annexin V-FITC/PI apoptosis and JC-1assays showed that SSe suppressed growth and migration,promoted apoptosis and decreased mitochondrial membrane potential of lung cancer cells.The results of q PCR indicated that SSe significantly decreased the expression of PDK and Bcl-2 and increased the expression of Bax and cytochrome c.The results of Western blot indicated that SSe significantly decreased the expression of p-p65,p65,p-IκBα,IκBα,PDK and Bcl-2,increased the expression of Bax and cytochrome c in lung cancer cells and reduced the release of p65 from the cytoplasm to the nucleus.NFκB/PDK axis was also further demonstrated by BAY11-7082 and p65 plasmid overpression to induce apoptosis of lung cancer cells.The lung cancer cell xenograft mouse model further demonstrated that SSe induced the apoptosis of lung cancer cells through the NFκB/PDK axis in vivo.Conclusion The present study,we explored the molecular mechanism of SSe inducing the apoptosis of lung cancer cells in vitro and in vivo,which SSe could target p65 to inactive NFκB signal pathway and further interfering with the expression of PDK and the proteins related to apoptosis,thus inhibiting glycolysis and inducing the apoptosis of lung cancer cells.These results highlight the potential of SSe as a chemotherapeutic agent for the clinical treatment lung cancer.