RGDS—GG—KLAKLAKK多肽对人骨肉瘤细胞黏附迁移和侵袭力的影响

The anti-tumor adhesive and metabolic activities of RGDS-GG-KLAKLAKK peptides on the human osteosarcoma cells

目的研究多肽RGDS—GG—KLAKLAKK对体外培养人骨肉瘤细胞MG-63黏附迁移和侵袭力的影响，并探讨其作用机制。方法将不同浓度（0、25、50、75、1130μmol／L）的多肽RGDS—GG-KLAKLAKK与MG-63细胞混合培养，用比色法测量多肽RGDS—GG-KLAKLAKK对MG-63细胞黏附力的抑制作用，通过transwell小室侵袭模型检测多肽对MG-63细胞侵袭力的影响。观测多肽对骨肉瘤细胞自发肺转移模型抗肿瘤转移的影响。结果MG-63骨肉瘤细胞对纤维连接蛋白（Fn）的黏附被多肽GDS—GG-KLAKLAKK对明显抑制（P〈0．05）。25、50、75、100μmol／L的多肽RGDS—GG—KLAKLAKK对MG-63细胞侵袭力的抑制率分别为（18．3±2．9）％、（28．5±4．8）％、（40．4±5．6）％和（66．7±7．8）％，对比空白对照组（0μmol／L多肽）差异有统计学意义（P〈0．05），多肽RGDS-GG-KLAKK对MG-63骨肉瘤细胞浸润能力有明显抑制作用。MG-63骨肉瘤细胞接种于裸鼠后给予多肽RGDS—GG—KLAKLAKK治疗，与对照组比较，有明显的肺重减轻、肺转移灶减少（P〈0．05）。结论多肽RGDS-GG-KLAKLAKK能够抑制人骨肉瘤MG-63细胞的体外黏附、侵袭和转移。

Objective To investigate the effects of the peptides （RGDS-GG-KLAKLAKK）on the invasion and metastasis ability of human osteosarcoma cell（MG-63）. Methods We co-cultivated the different concentrations of the peptides RGDS-GG-KLAKLAKK （ concentration separately as 0,25,50,75, 100 μmol/L） with the MG-63 cell. Cell adhesion and cell invasion assay both in vitro and in vivo were used to investigate the inhibitory effects on MG-63 adhesion to fibronectin （Fn） coated surface. Transwell was used to assay the effect of RGDS-GG-KLAKLAKK on MG-63 cell invasive capability on reformed basement membrane. The effect of anti-metastatic peptides was observed in the MG-63 cell model that will automatically metastasize to lung. Results RGDS-GG-KLAKLAKK obviously suppressed the cell adhesion to fibronectin in a dose-dependent manners （ P 〈 0. 05 ）. After MG-63 cells were treated with peptides of 25,50,75,100 μmol/L for 48 h, the inhibitory ratios of invasion were （ 18.3 ± 2.9） %, （28.5 ± 4.8 ） %, （40.4 ± 5.6） % and （ 66.7 ± 7.8 ） %, respectively （ P 〈 0.05 ）. MG-63 cells was implantated in node mice. RGDS-GG-KLAKLAKK treatment were done to each mice by 50,100 μmol/L, the lung metastatic nodule number and the weight of metastatic lung could be decreased significantly （ P 〈 0.05 ）. Conclusion The pepetdes RGDS-GG-KLAKLAKK can suppress the invasive and metastatic activities of human osteosarcoma Cell line MG-63.