摘要Objective:Chronic inflammation plays a fatal role in tumor metastasis.Pterostilbene(PTE)is a natural dimethylated analogue of resveratrol with anticancer and anti-inflammatory activities.This study aimed to investigate the inhibitory effect of PTE on inflammation-associated metastasis and explore the under-lying mechanisms.Methods:Lipopolysaccharide(LPS)-induced lung inflammation and melanoma metastasis models were established in mice.After PTE treatment for four weeks,the organ index,histological changes,proinflam-matory cytokines,and the expression and activity of neutrophil elastase(NE),a biomarker of neutrophil influx in the lungs,were analysed.Additionally,direct effects of PTE on NE-induced B16 cell migration were explored in wound healing and Transwell assays,and the expression of thrombospondin-1(TSP-1)and epithelial-mesenchymal transition(EMT)markers were also detected.Results:PTE obviously attenuated the LPS-induced metastasis of circulatory B16 cells to lungs by reduc-ing the number of metastatic nodules on the lung surfaces and the lung weight/body weight ratio.PTE treatment also significantly reduced LPS-activated increase levels of tumor necrosis factor(TNF)-α and interleukin(IL)-6 in the lungs of tumor-bearing mice.In addition,increased expression and enzyme activ-ity of NE and decreased expression of TSP-1 were observed,and these were blocked by PTE.In vitro,PTE at concentrations without cytotoxicity also markedly suppressed NE-triggered B16 cell migration,pre-vented NE-induced TSP-1 proteolysis and reversed the expression of vimentin,N-cadherin and E-cadherin.Conclusion:PTE could block inflammation-enhanced tumor metastasis,and the underlying mechanism might be associated with the inhibition of NE-mediated TSP-1 degradation.