title: Suppression of metastasis of human pancreatic cancer cells to the liver by small interfering RNA-mediated targeting of the midkine gene.
abstract: The present study aimed to ascertain whether suppression of midkine (MK) expression in pancreatic cancer cells inhibits metastasis to the liver. Human pancreatic cancer AsPC-1 cells were transfected with small interfering RNA (siRNA) targetingMK. siRNA againstMKwas observed to reduce the expression of MK mRNA and protein in a concentration- and time-dependent manner, and to decrease the number of migrating and tissue-penetrating cells in a concentration-dependent manner (P<0.005). Extracellular vascular endothelial growth factor (VEGF) concentrations were markedly reduced for the siRNA-transfected cells compared with those that were non-siRNA-transfected. The liver transmission rate and tumor nodule number in the animals harboring the siRNA-transfected cells were lower compared with those in the animals harboring the non-siRNA-transfected cells (P<0.005). These data indicate that metastasis of pancreatic cancer cells to the liver requires the expression of MK. The downregulation of VEGF expression is essential to the mechanism whereby suppression of MK expression constrains the metastasis of pancreatic cancer cells to the liver.
authors.affiliation: Zhenjiang Key Laboratory of Molecular Endocrinology, Zhenjiang, Jiangsu 212001, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Yu
authors.initials: Y
authors.lastname: Fan
authors.forename: Baoding
authors.initials: B
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.forename: Yina
authors.initials: Y
authors.lastname: Gao
authors.forename: DA
authors.initials: D
authors.lastname: Wei
keywords: AsPC-1 cells; liver metastasis; midkine; pancreatic cancer; small interfering RNA; vascular endothelial growth factor