Butyrate inhibits pancreatic cancer invasion

Pancreatic cancer is the most deadly gastrointestinal malignancy because of its propensity for local invasion and early metastasis. Integrin chains, in particular P4, can promote invasion in other cancers. The effect of sodium butyrate (NaBT), which induces differentiation in transformed cells, on integrin expression is unknown. The purpose of this study was to determine patterns of integrin expression in pancreatic cancer cells and investigate the effect of NAT on integrin expression and invasion. Integrin expression was assessed in the less invasive MIA-PaCa-2 and PANC-1 and more invasive L3.6, AsPC-1, and SUIT-2 human pancreatic cancer cell lines by ribonuclease (RNase) protection assay. Western blotting and immunofluorescent staining for P4 expression was determined after NaBT treatment. Matrigel invasion chambers were used to assess pancreatic cancer cell invasion. beta4 and beta7 integrin expression was highest in L3.6, AsPC-1, and SUIT-2 cells. NOT reduced the expression of beta4 integrin in AsPC-1 cells including less cell surface beta4. Invasion of AsPC-1 cells was also reduced by NaBT. Expression of 04 is higher in more aggressive pancreatic cancer cells; NAT inhibits P4 expression and invasion. NaBT may represent a novel strategy to inhibit pancreatic cancer invasion and improve the prognosis of this deadly disease. (C) 2003 The Society for Surgery of the Alimentary Tract