Propofol affects the growth and metastasis of pancreatic cancer via ADAM8.

Abstract

Anesthesia is a major component of surgery and recently considered an important regulator of cell phenotypes. Here we aimed to investigate propofol, an anesthesia drug, in suppressing pancreatic cancer (PDAC), focusing on A disintegrin and metalloprotease 8, (ADAM8) as a molecular mediator. Quantitative real-time PCR and western blot were used to assess the change of ADAM8 expression in Panc1 PDAC cells treated with 5 or 10μg/mL propofol, using cells treated with BB-94 inhibitor as controls. ADAM8 activity was measured through quantifying fluorescence release induced by PEPDAB013 decomposition. MTT assay, scratch wound assay and Matrigel invasion assay were used to investigate the proliferation, migration and invasion of the cells. Western blot and immunohistochemical analysis were used to quantify integrin β1, ERK1/2, MMP2 and MMP9 expression. Propofol and BB-94 reduced ADAM8 expression, cell proliferation and migration of Panc1 cells. Tumor growth was inhibited by propofol and BB-94, concomitant with downregulation of integrin β1, ERK1/2, MMP2 and MMP9. ADAM8 is downregulated by propofol, leading to inhibition of pancreatic cancer proliferation and migration. Pancreatic tumor growth is also inhibited by propofol and BB-94, which is attributed to suppression of ERK/MMPs signaling.