E-选择素在结肠癌肝转移作用中的实验研究

The Effects of E-selectin on the Liver Metastasis of Colon Carcinoma

目的探讨E-选择素在结肠癌肝转移中的作用,并筛选有临床应用前景的抗结肠癌转移药物。方法检测E-选择素在肝静脉内皮细胞(ED25)中的表达,检测活化ED25与结肠癌细胞Love、肝癌细胞HepG2、鼻咽癌细胞在体外的黏附差异,并测试不同药物对黏附的影响。结果E-选择素高强度表达于活化后的ED25,且能介导Love与ED25的黏附。Love条件培养液处理ED25可增强与Love、HepG2、鼻咽癌细胞的黏附,但Love和HepG2与ED25的黏附明显强于鼻咽癌细胞(P<0.05),而Love和HepG2与ED25的黏附差异无显著性意义(P=0.29);抗E-选择素抗体、地塞米松、丝裂霉素、5-FU有较强抑制结肠癌细胞与ED25黏附作用。结论E-选择素可促进结肠癌细胞与ED25的黏附;结肠癌细胞可分泌促进ED25表达E-选择素表达的物质,从而促进了结肠向肝脏癌的转移;地塞米松、丝裂霉素、5-FU可以抑制结肠癌细胞与ED25的黏附,有望成为预防结肠癌肝转移的药物。

Objective To explore the role of E-selectin on the liver metastasis of colon carcinoma and select possible drugs to inhibit metastasis of colon carcinoma. Methods Expression of E-selectin in hepatic vein endothelial cell （ED25） was detected. The adherence ability of actived ED25 to colon carcinoma cell （Love）,hepatocellular carcinoma cell （HepG2） and nasopharyngeal carcinoma cell were compared in vitro by solid phase adhesion assay. The effect on the tumor cell endothelial adhesion was investigated in different drugs. Results Eselectin was highly expressed on the surface of actived ED25 and could mediate the adhesion of ED25 to Love. The adherence ability was enhanced after ED25 stimulated by Love condition medium in different tumor cells. The adherence ability of actived ED25 to Love and HepG2 were significant higher than that of nasopharyngeal carcinoma cell （P〈0.05）,while there had no difference in the adherence ability of actived ED25 to Love and HepG2 （P = 0. 29）. Anti-E-selectin antibody,dexamethasone,mitomycin and 5-FU were able to block the adhesion of Love to ED25. Conclusion E-selectin is an important molecular in the adhesion of Love to ED25,and colon carcinoma cell can secrete some factorsto promote the expression of E-selectin. Dexamethasone, mitomycin and 5-FU could inhibit the adhesion of Love to ED25, and could be hopeful drugs in inhibiting the metastasis of colon carcinoma.