Inhibition of human pancreatic cancer by β ₂-adrenergic antagonist via suppression of invasion

Objective: To study the effect of β ₂ adrenergic antagonist on the proliferation and invasiveness of pancreatic cancer cell line and its action mechanism. Methods: The cancer cell proliferation was determined by MTT assay; the cancer cell invasion was detected by transwell assay; the cell cycle distribution was determined by the flow cytometry assay; the activation of NF-κB and AP-1 was measured by electrophoretic mobility shift assays; and the protein expression of VEGF, COX-2, MMP-2 and MMP-9 was analyzed by Western blot. Results: β ₂-adrenergic antagonist ICI118551 and β _1/2-adrenergic antagonist propranolol significantly induced G ₁/S phase arrest and apoptosis and suppressed cell invasion and proliferation as compared to β ₁-adrenergic antagonist metoprolol and control. In our study, β ₂-adrenoceptor antagonists inhibited activation of transcription factors NF-κB and AP-1. Moreover, β ₂-adrenoceptor antagonist therapy significantly altered VEGF, COX-2, MMP-2 and MMP-9 expressions. The effect of the ICI118, 551 was stronger in BxPC-3 cell line than in MIA PaCa-2 cell line. Conclusion: β ₂-adrenergic antagonists could suppress invasion and proliferation by inhibiting activation of NF-κB and AP-1 as well as expression of its target genes, such as MMP-9, MMP-2, VEGF and COX-2.