内皮抑素联合异环磷酰胺对小鼠肉瘤血管生成及肿瘤生长的抑制作用

The inhibitory effect of endostatin combined with ifosfamide chemotherapy on angiogenesis and tumor growth of sarcoma in mice

目的:观察内皮抑素(endostatin,ES)联合异环磷酰胺(ifosfamide,IFO)对小鼠肉瘤皮下移植模型中肿瘤血管生成和肿瘤生长的抑制作用。方法:建立小鼠肉瘤模型,随机将60只荷瘤小鼠分为对照组、ES组、IFO组和ES+IFO联合用药组,分别给予相应药物,观察肿瘤生长情况,计算抑瘤率,并且采用免疫组织化学法检测肿瘤微血管密度(microvessel density,MVD)。动物处死前1 min于尾静脉注射DiOC7(3),荧光显微镜下观察肿瘤组织灌注血管标记,计算灌注血管平均距离。结果:各治疗组药物均能明显抑制肿瘤的增长,ES组、IFO组和ES+IFO组的抑瘤率分别为43.13%、76.57%和84.66%,联合用药组的抑瘤作用最为显著(P<0.05)。对照组、ES组、IFO组与ES+IFO联合用药组的移植瘤组织MVD分别为(43.13±9.86)、(17.87±7.69)、(29.20±9.28)及(7.60±3.18)个/400 Hp,灌注血管平均距离分别为(43.33±8.21)、(84.94±6.99)、(68.96±10.90)及(121.08±22.75)μm,联合用药组的MVD和灌注血管平均距离与单一用药组及对照组相比的差异有统计学意义(P<0.05)。结论:ES联合IFO治疗肉瘤时,可通过显著抑制结构血管和灌注血管生成来抑制肿瘤生长,联合用药效果优于单一用药,二者具有协同抗肿瘤作用。

Objective:To evaluate the inhibitory effect of endostatin(ES) combined with ifosfamide(IFO) on the angiogenesis and growth of transplanted sarcoma in mice.Methods:To establish the sarcoma model in mice,the sixty mice bearing sarcoma were randomly divided into the control group,ES group,IFO group,and ES+IFO group.The mice in treatment group were administered ES,IFO,or ES+IFO,respectively.The tumor growth was observed in each group and immunohistochemical method was employed to examine the microvessel density(MVD).DiOC7(3) was injected via tail vein at 1 min before the mice were sacrificed.The fluorescence markers of tumor tissues were observed under fluorescence microscope and the average distance of perfused vessels was calculated.Results:The tumor growth was significantly inhibited in ES,IFO,and ES+IFO groups,with the inhibitory rates of 43.13%,76.57%,and 84.66%,respectively(P<0.05).The value of MVD was(43.13±9.86),(17.87±7.69),(29.20±9.28),and(7.60±3.18) per 400 Hp and the average distance of perfused vessels was(43.33±8.21),(84.94±6.99),(68.96±10.90),and(121.08±22.75) μm in the control group,ES group,IFO group,and ES+IFO group,respectively.The MVD value and the average distance perfused vessel had significant difference in ES+IFO group compared with the control group,ES group,IFO group(P<0.05).Conclusion:ES combined with IFO has synergistic effect on inhibiting the growth of transplanted sarcoma in mice via suppressing the formation of anatomic vessels and perfused vessels.The curative effect of combined therapy was better than single drug therapy.