Abstract:Objective: To investigate the role and mechanism of Wnt1 induced secreted protein1(WISP1) in invasion and metastasis of esophageal squamous cell carcinoma. Methods: Human esophageal squamous cell carcinoma cells(ESCC), Eca109 and TE8, and normal human esophageal epithelial cells, Het1a, were cultured in vitro. RTPCR and Western blotting were used to detect the expression of WISP1 between ESCCs and Het1a cells. Eca109 and TE8 cells were divided into blank control, negative control and WISP1 siRNA groups. The cell proliferation was detected by CCK8 method. Flow cytometry was used to analyze the apoptosis rate of each group. Transwell assay was used to detect the ability of invasion. The expression of VEGFA, VEGFC, MMP2 and MMP9 in each group was detected by Western blotting. The secretion of VEGFC and MMP9 were detected by ELISA. The expression changes of NFκB pathway were determined by Western blotting. Results: WISP1 were highly expressed in ESCCs compared with Het1a cells(P<0.01). CCK8 and flow cytometry results showed that the proliferation of ESCCs were significantly inhibited by downregulation of WISP1(P<0.05), while had no significant effect on the apoptosis. The results of Western blotting and ELISA showed that, even though there were no significant change of VEGFA and MMP2, the expression or secretion of VEGFC and MMP9 were downregulated after siRNAWISP1 treatment(P<0.05). Downregulation of WISP1 could significantly reduce the phosphorylation of NFκBp65 and induce the phosphorylated IκBα(pIκBα), but had no effect on the total expression of NFκB and IκBα. Conclusion: WISP1 promotes the invasion and metastasis of ESCC via NFκB pathway.
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