Effect of aprepitant on epithelial-mesenchymal transformation in non-small cell lung cancer through inhibiting SFN protein

Objective To investigate the regulatory effects of stratifin(SFN) on the epithelial-mesenchymal transformation, migration, and invasion of non-small cell lung cancer A549 cells, and the effects of aprepitant on SFN function.Methods First, siSFN-1, siSFN-2, SFN and NC genes were transferred into A549 cells by transient transfection. The expression of SFN, E-cadherin, N-cadherin and vimentin were detected by Western blot. The cell migration and invasion were detected by the wound healing assay and Transwell assay. The regulatory effect of aprepitant on the proliferation of SFN-overexpressed A549 cells was measured by CCK8 assay at 24, 48 h and 72 h.According to the IC50 value measured by CCK8 assay, the expression of SFN, E-cadherin, N-cadherin, vimentin in A549 cells overexpressing SFN for 48 h, as well as cell migration and invasion changes were further explored after treatment with aprepitant at the concentrations of 16, 8μmol/L and 4 μmol/L.Results In the cell proliferation-toxicity test at 24, 48 h and 72 h, with the extension of aprepitant treatment time, the cell proliferation ability showed a gradual decline, with significant drug inhibitory effect(P<0.05).Wound healing assay results showed that the migration distance of SFN transfected A549 cells was significantly longer than that of the NC, siSFN-1 and siSFN-2 groups(P<0.05).The migration distance of the placebo group was longer than that of the 16, 8 μmol/L and 4 μmol/L aprepitant group, and the migration distance of the cells in the 16, 8 μmol/L and 4 μmol/L aprepitant groups gradually increased with the decrease of the concentrations(P<0.05).In Transwell migration and invasion experiments, the number of migrated and invaded A549 cells transfected with SFN was more than those in the NC, siSFN-1 and siSFN-2 groups(P<0.05).The number of migrated and invaded cells in the placebo group was more than those in the 16, 8 μmol/L and 4 μmol/L aprepitant groups, and the number of migrated and invaded cells in the 16, 8 μmol/L and 4 μmol/L aprepitant groups gradually increased with the decrease of concentrations(P<0.05). According to Western blot analysis, overexpression of SFN decreased the epithelial markers E-cadherin and increased the interstitial markers N-cadherin and vimentin(P<0.05).Theplacebo group showed decreases in E-cadherin, and increases in N-cadherin and vimentin, compared with the three other groups, and E-cadherin increased and N-cadherin decreased with the increase of concentrations intheAprepitant group(P<0.05).Conclusions SFN overexpression can promote epithelial mesenchymal transformation, migration and invasion in non-small cell lung cancer.Aprepitant can inhibit SFN expression and thereby inhibit its mediated epithelial mesenchymal transformation, migration and invasion.