抗黏附多肽对人肝癌高转移细胞系MHCC97侵袭转移的抑制作用

Inhibitory effects of anti-adhesion peptides on invasion/metastasis ability of hepatocellular carcinoma cells

目的 研究抗黏附多肽GRGDS、YIGSR对人肝癌高转移细胞系MHCC97侵袭转移的抑制作用。方法 选择GRGDS、YIGSR作为抗黏附多肽 ,选具有高转移潜能的人肝癌细胞系MHCC97为靶细胞。用体外细胞 基质黏附实验检测两种多肽对MHCC97细胞对所包被的纤维连接蛋白 (FN)的黏附抑制作用 ;用体外细胞侵袭实验检测两种多肽对MHCC97细胞的侵袭抑制作用。结果 GRGDS、YIGSR对MHCC97细胞对FN黏附的抑制作用呈时间剂量依赖。当药物浓度达 2 0 0mg/L时 ,黏附抑制率达 60 %。两种多肽分别与细胞共育 48h后 ,均显示出明显的侵袭抑制能力。将细胞接种于裸鼠后给予GRGDS或YIGSR治疗 ,与对照组比较 ,有明显的肺重减轻、肺转移灶减少 (P <0 .0 5 )。结论 抗黏附多肽GRGDS、YIGSR对人肝癌高转移细胞系MHCC97具有明显抑制黏附、抑制侵袭转移的作用。

Objective To study the inhibitory effects of anti-adhesion peptides,GRGDS,YIGSR on invasion and metastasis ability of hepatocellular carcinoma cells.Methods Synthetic peptides with the sequence of GRGDS or YIGSR were selected as the anti-adhesion peptides,and cultured hepatocellular carcinoma cell line with higher metastasis potential MHCC97 was employed in this experiment.Cell adhesion and cell invasion assay both in vitro and in vivo were used to investigate the inhibitory effects on MHCC97 adhesion to fibronectin (FN) coated surface,and to observe the blockage of MHCC97 invasion using Bodey chamber,packed with matrigel or through the numbers of metastatic lung foci in vivo.Results (1) Anti-adhesion peptides,GRGDS/YIGSR,can inhibit cell adhesion to fibronectin in a dose- and time-dependent manner.As the concentration of peptides reached to 200 mg/L,the inhibitory rate of cell adhesion to fibronectin surface was up to 60%.(2) The result documented marked anti-invasive effects after human hepatocellular carcinoma cell line with high metastasis potential was co-incubated with GRGDS/YIGSR in the concentration of 100 mg/L for 48 h,respectively.(3) After the cells of human hepatocellular carcinoma with high metastasis potential was implantated in node mice,GRGDS/YIGSR-treatment were done to each mice by 100 mg/ 0.2 L on the day of 3,5,7,9,11,13,15,17,19,21 respectively.Lung weight was lowered and the number of metastatic nodes was reduced as compared with control group.Conclusion Anti-adhesion peptides,GRGDS/YIGSR,have marked inhibitory effects on adhesion and metastasis of human hepatocellular carcinoma cell line with high metastasis potential.