Ulinastatin Inhibits Nasopharyngeal Carcinoma Metastasis by Suppressing uPA/uPAR Signaling

Background: Distant metastasis is the main reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we evaluated the effect of ulinastatin (UTI) on NPC metastasis and investigated its underlying mechanism.Methods: Highly-metastatic NPC cell lines S18 and 5-8F were treated with UTI and the effect on cellular growth, migration, and invasion of NPC cells was determined using MTS and transwell assays. The luciferase-expressing S18 cells (S18-1C3) were injected into the left hind footpad of nude mice to establish a spontaneous footpad to popliteal lymph node (LN) metastasis model. The luciferase mRNA was measured by qPCR to calculate the metastatic inhibition rate. The UTI-related uPA, uPAR and the main molecular members of the JAT/STAT3 pathway were detected by qPCR and immunoblotting.Results: UTI inhibited the migration and invasion of S18 and 5-8F cells with no effect on cellular growth in vitro, and suppressed metastasis of S18 cells in vivo. uPAR expression was reduced from 24 to 48 hours after UTI treatment. The anti-metastasis effect of UTI partially relies on the suppression of uPA and uPAR.Conclusion: UTI partially inhibits NPC metastasis via downregulating the expression of uPA and uPAR.