Background: Integrin alpha v beta 6 is up-regulated in a variety of human carcinomas and plays a crucial role in tumor invasion and metastasis. However, the function of alpha v beta 6 in pancreatic carcinoma and its potential role in gemcitabine resistance remain unknown. Materials and Methods: Small interfering RNA (siRNA) targeting at,06 was constructed and transfected into PANC-1 cells. Effects of alpha v beta 6 knockdown on cell proliferation, invasion, cell cycle progression, apoptosis and chemosensitivity to gemcitabine were investigated. Results: Expression of alpha v beta 6 in PANC-1 cells was markedly suppressed by siRNA. Silencing of alpha v beta 6 expression significantly inhibited cell proliferation and invasiveness, resulted in cell cycle at-rest, and induced cell apoptosis. More importantly, alpha v beta 6 knockdown enhanced chemosensitivity to gemcitabine and increased gemcitabine-induced caspase-mediated apoptosis. Conclusion: These findings suggest a novel mechanism by which alpha v beta 6 contributes to pancreatic carcinoma progression. The combination of alpha v beta 6 silencing and gemcitabine treatment may provide an effective therapeutic strategy for highly resistant pancreatic carcinoma.
