〔Abstract〕 To investigate the potential of bortezomib in inhibiting the malignant biological behaviors and liver metastasis of pancreatic cancer cells . Methods KPC and Panc02 cell lines were used as a couple of working cells in this study . The CCK-8 assay was used to assess the effect of bortezomib on cell viability in murine pancreatic cancer cells , and the half inhibitory concentration ( IC50 ) values were calculated . The EdU assay was performed to evaluate the impact of bortezomib on the proliferation of these two cell lines . Apoptosis assays were conducted to investigate the pro-apoptotic effects of bortezomib on pancreatic cancer cells . Colony formation , scratch wound healing , and Transwell assays were used to examine the effects of bortezomib on the proliferation , migration , and invasion of pancreatic cancer cells . QRT-PCR and Western blot were employed to assess the impact of bortezomib on the expression of epithelial-mesenchymal transition ( EMT) related markers , including Cdh1 , Cdh2 , Vim and Snail gene and E-cadherin protein , N-cadherin protein , Vimentin protein and Snail protein . An in vivo spleen-to-liver metastasis model was established to evaluate the therapeutic value of bortezomib in inhibiting pancreatic cancer liver metastasis . Results The CCK-8 assay showed that bortezomib significantly reduced the via- bility of KPC and Panc02 cells (P < 0. 000 1) , with IC50 values of approximately 118. 70 nmol/L and 34. 16 nmol/ L , respectively . The EdU assay showed that bortezomib markedly inhibited the proliferative capacity of pancreatic cancer cells (P < 0. 01) . Apoptosis assays showed that bortezomib promoted both early and late apoptosis in pan- creatic cancer cells (P < 0. 05) . Colony formation , scratch wound healing , and Transwell assays showed that bort- ezomib effectively suppressed colony formation ( P < 0. 01) , migration , and invasion ( P < 0. 01) of pancreatic cancer cells . qRT-PCR and Western blot analyses showed that bortezomib altered the expression of EMT-related markers at both the mRNA ( the expression level of Cdh1 gene increased , while the expression levels of Cdh2 , Vim and Snail genes decreased . ) ( P < 0. 000 1) and protein ( the expression level of E-cadherin protein increased , while the expression levels of N-cadherin protein , Vimentin protein and Snail protein decreased) levels in pancreat- ic cancer cells . The in vivo spleen-to-liver metastasis model demonstrated that bortezomib significantly inhibited pancreatic cancer liver metastasis ( P < 0. 01) . Conclusion Bortezomib can inhibit the malignant biological be- haviors of pancreatic cancer cells , suggesting it might be a potential anti-cancer drug in pancreatic cancer.