Cooperative inhibitory effects of antisense oligonucleotide of cell adhesion molecules and cimetidine on cancer cell adhesion

摘要： <正> AIM:To explore the cooperative effects of antisenseoligonucleotide (ASON) of cell adhesion molecules andcimetidine on the expression of E-selectin and ICAM-1 inendothelial cells and their adhesion to tumor cells.METHODS:After treatment of endothelial cells with ASONand/or cimetidine and induction with TNF-α,the proteinand mRNA changes of E-selectin and ICAM-1 in endothelialcells were examined by flow cytometry and RT-PCR,respectively.The adhesion rates of endothelial cells to tumorcells were measured by cell adhesion experiment.RESULTS:In comparison with TNF-α inducing group,lipo-ASON and lipo-ASON/cimetidine could significantly decreasethe protein and mRNA levels of E-selectin and ICAM-1 inendothelial cells,and lipo-ASON/cimetidine had mostsignificant inhibitory effect on E-selectin expression (from36.37±1.56% to 14.23±1.07%, P<0.001).Meanwhile,cimetidine alone could inhibit the expression of E-selectin(36.37±1.56% vs 27.2±1.31%,P<0.001),but not ICAM-1(69.34±2.50% vs 68.07±2.10%,P<0.05)and the two kinds ofmRNA,either.Compared with TNF-α inducing group,the rateof adhesion was markedly decreased in lipo-E-selectin ASONand lipo-E-selectin ASON/cimetidine treated groups(P<0.05),and lipo-E-selectin ASON/cimetidine worked better thanlipo-E-selectin ASON alone except for HepG2/ECV304 group(P<0.05).However,the decrease of adhesion was notsignificant in lipo-ICAM-1 ASON and lipo-ICAM-1 ASON/cimetidinetreated groups except for HepG2/ECV304 group (P>0.05).CONCLUSION:These data demonstrate that ASON incombination with cimetidine in vitro can significantly reducethe adhesion between endothelial cells and hepatic orcolorectal cancer cells,which is stronger than ASON orcimetidine alone.This study provides some useful proofsfor gene therapy of antiadhesion. ... （共5頁）