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首页> 外文期刊>World Journal of Gastroenterology >Cooperative inhibitory effects of antisense oligonucleotide of cell adhesion molecules and cimetidine on cancer cell adhesion
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Cooperative inhibitory effects of antisense oligonucleotide of cell adhesion molecules and cimetidine on cancer cell adhesion

机译：细胞粘附分子和西咪替丁反义寡核苷酸对癌细胞粘附的协同抑制作用

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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, lipo-ASON 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% vs 68.07+-2.10%, P>0.05) and the two kinds of mRNA, 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/cimetidine 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 endothelial 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.
机译：目的：探讨细胞粘附分子和西咪替丁的反义寡核苷酸（ASON）对内皮细胞中E-选择素和ICAM-1表达及其与肿瘤细胞粘附的协同作用。方法：用ASON和/或西咪替丁处理内皮细胞并用TNF-α诱导后，通过流式细胞术和RT-PCR分别检测内皮细胞中E-选择素和ICAM-1的蛋白质和mRNA的变化。通过细胞粘附实验测量内皮细胞对肿瘤细胞的粘附率。结果：与TNF-α诱导组相比，脂质-ASON和脂质-ASON /西咪替丁可明显降低内皮细胞中E-选择素和ICAM-1的蛋白质和mRNA水平，其中脂质-ASON /西咪替丁具有最显着的抑制作用。对E-选择素表达的影响（从36.37 + -1.56％到14.23 + -1.07％，P <0.001）。同时，单独的西咪替丁可以抑制E-选择素的表达（36.37 + -1.56％vs 27.2 + -1.31％，P <0.001），但不能抑制ICAM-1（69.34 + -2.50％vs 68.07 + -2.10％，P> 0.05）和两种mRNA。脂质E-选择素ASON和脂质E-选择素ASON /西咪替丁治疗组与TNF-α诱导组相比，黏附率明显降低（P <0.05），脂质E-选择素ASON /西咪替丁治疗效果更好。与HepG2 / ECV304组相比，单独使用lipo-E-selectin ASON的患者（P <0.05）。然而，除了HepG2 / ECV304组，在lipo-ICAM-1 ASON和lipo-ICAM-1 ASON /西咪替丁治疗的组中粘附力的降低并不显着（P> 0.05）。结论：这些数据表明，ASON与西咪替丁联用可显着降低内皮细胞与肝癌或结直肠癌细胞之间的粘附，其强度比单独使用ASON或西咪替丁强。该研究为抗粘连的基因治疗提供了一些有用的证据。

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