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

• Published in: World journal of gastroenterology : WJG Vol. 10; no. 1; pp. 62 - 66
• Main Authors: Tang, Nan-Hong, Chen, Yan-Ling, Wang, Xiao-Qian, Li, Xiu-Jin, Yin, Feng-Zhi, Wang, Xiao-Zhong
• Format: Journal Article
• Language: English
• Published: United States Hepato-Biliary Surgery Institute of Fujian Province,Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China%Gastroenterology Department, Union Hospital,Fujian Medical University, Fuzhou 350001, Fujian Province, China 2004; Baishideng Publishing Group Inc
• Subjects: Cell Adhesion - drug effects; Cell Line, Tumor; Cimetidine - pharmacology; Colorectal Neoplasms; E-Selectin - genetics; Electrophoresis, Agar Gel; Endothelium - cytology; Gene Expression; Histamine H2 Antagonists - pharmacology; Humans; Intercellular Adhesion Molecule-1 - genetics; Liver Cancer; Liver Neoplasms; Oligonucleotides, Antisense - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; 反义核苷酸; 甲氰咪胍; 细胞因子; 细胞粘附分子; 肿瘤抑制; 肿瘤细胞
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v10.i1.62

AIM: To explore the cooperative effects of antisense oligonucleotide (ASON) of cell adhesion molecules and cimetidine on the expression of E-selectin and ICAM-1 in endothelial cells and their adhesion to tumor cells. METHODS: After treatment of endothelial cells with ASON and/or cimetidine and induction with TNF-α, the protein and mRNA changes of E-selectin and ICAM-1 in endothelial cells were examined by flow cytometry and RT-PCR,respectively. The adhesion rates of endothelial cells to tumor cells were measured by cell adhesion experiment. RESULTS: In comparison with TNF-α inducing group, lipoASON and lipo-ASON/cimetidine could significantly decrease the protein and mRNA levels of E-selectin and ICAM-1 in endothelial cells, and lipo-ASON/cimetidine had most significant inhibitory effect on E-selectin expression (from 36.37±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% vs68.07±2.10%,P>0.05)and the two kinds ofmRNA, either. Compared with TNF-α inducing group, the rate of adhesion was markedly decreased in lipo-E-selectin ASON and lipo-E-selectin ASON/cimetidine treated groups(P<0.05),and lipo-E-selectin ASON/cimetidine worked better than lipo-E-selectin ASON alone except for HepG2/ECV304 group(P<0.05). However, the decrease of adhesion was not significant in lipo-ICAM-1 ASON and lipo-ICAM-1 ASON/dmetidine treated groups except for HepG2/ECV304 group (P >0.05). CONCLUSION: These data demonstrate that ASON in combination with cimetidine in vitro can significantly reduce the adhesion between endc~thelial cells and hepatic or colorectal cancer cells, which is stronger than ASON or cimetidine alone. This study provides some useful proofs for gene therapy of antiadhesion.