【摘要】 目的　了解血管内皮细胞生长因子 (vascularendothelialgrowthfactor,VEGF)可溶性受体sFlt 1联合内皮抑素 (Endostatin ,ES)基因治疗对甲状腺滤泡状癌细胞生长的影响 ,并探讨其作用机理。方法　 2 0 0 1年 6月至 2 0 0 3年 12月 ,采用表达ES的肿瘤细胞系FTC133 rvEndo和表达sFlt 1的 2 93 Flt1 3d细胞行动物实验 ,观察肿瘤在裸鼠模型中的生长状况。用抗CD31抗体对肿瘤切片进行免疫组织化学染色检测微血管 ,计算微血管密度 (microvesseldensity ,MVD)。检测血清中ES和VEGF浓度。结果　在裸鼠模型中 ,种植 2 8d后 ,抑瘤率sFlt1组为 70 37% ,sFlt1+ES组为 93 4 9%。免疫组化染色表明对照组MVD为 (10 2 71± 13 14 ) ;而sFlt1组为(40 76± 12 6 5 ) ,sFlt1+ES组为 (13 71± 6 2 7) ,各组间差异有显著性 (P <0 0 5 )。对照组带瘤鼠血清中人VEGF浓度为 (31 2 5± 6 2 1) pg ,而sFlt1组为每毫升 (10 5 9± 0 72 ) pg ,sFlt1+ES组为每毫升 (7 4 5± 0 81) pg ,后两者与对照组间差异有显著性 (P <0 0 5 )。结论　sFlt1和ES的联合应用可增强其抗肿瘤血管生成和抗甲状腺滤泡状癌肿瘤生长的作用。其机理可能与VEGF的受抑制有关。更多还原

【Abstract】 Objective To evaluate the combinative effect of endostatin (ES) and sFlt-1 on the in vivo growth of a follicular thyroid carcinoma(FTC) cell line FTC133. Methods Fifteen nude mice were divided into three groups. Mice in control group were injected with FTC133 cells and 293-LacZ cells;mice in the sFlt1 group were injected with FTC133 cells and 293-sFlt1 cells;mice in the sFlt1+ES group were injected with FTC133-rvEndo cells and 293-sFlt1 cells. Tumor volumes were monitored. After the mice were sacrificed, the tumors were stained immunohistochemically (IHC) using anti-CD31 antibody and microvessel density (MVD) was calculated. The serum concentrations of human VEGF and murine ES were detected. Results At the 28th day after inoculation, compared to control group, the tumor inhibition rate for sFlt1 group was 70.37% and that for sFlt1+ES group was 93.49%. IHC staining showed MVD in sFlt1 group was (40.76±12.65) and that of sFlt1+ES group was (13.71±6.27), which was significantly lower than that in control group(P<0.05). The serum concentration of human VEGF in sFlt1 group was (10.59±0.72)pg/mL while that in sFlt1+ES group was (7.45±0.81)pg/mL,which were significantly lower than that in control group, (31.25±6.21)pg/mL(P<0.05). Conclusion sFlt1 inhibites FTC xenografts through its antiangiogenic effect. Inhibitory effect can be enhanced when combining with endostatin gene transduction. The effect may be related to inhibition of the secretion of VEGF in tumor cells.更多还原