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目的探讨血管内皮细胞生长因子(VEGF)反义寡核苷酸和低分子肝素法安明单用或联用对小鼠Lewis肺癌生长、转移的抑制作用。方法复制小鼠Lewis肺癌模型40只,随机分为对照组、VEGF反义寡核苷酸(ASODN)组、VEGF错义寡核苷酸(MSODN)组、低分子肝素(LMWH)组及联合治疗组,每组8只,分别给予生理盐水、VEGF-ASODN、VEGF-MSODN、法安明及VEGF-ASODN+法安明皮下注射,隔日1次,共15次。检测皮下移植瘤变化和肺转移率;应用免疫组织化学的方法检测肿瘤组织微血管密度(MVD);应用Western印迹的方法检查肿瘤组织VEGF蛋白表达。结果ASODN、LMWH和联合治疗组的抑瘤率分别为47·34%、27·31%和59·03%;肺转移率分别为37·5%、37·5%和25%;MVD和VEGF蛋白表达降低;与对照组和MSODN组相比,抑瘤率和MVD差异均有统计学意义(P<0·05)。结论VEGF-ASODN和法安明具有下调VEGF表达,抗血管生成作用;二者联合有协同抗肿瘤作用。
Objective To investigate the inhibitory effect of antisense oligonucleotide of vascular endothelial growth factor (VEGF) and low molecular weight heparin on the growth and metastasis of Lewis lung carcinoma in mice. Methods Forty mouse Lewis lung carcinoma models were randomly divided into control group, VEGF antisense oligonucleotide (ASODN) group, VEGF missense oligonucleotide (MSODN) group, low molecular weight heparin (LMWH) group and combination therapy The rats in each group were injected with normal saline, VEGF-ASODN, VEGF-MSODN, Fahrenk and VEGF-ASODN + fenamin subcutaneously once daily for 15 times. The changes of subcutaneous xenografts and the rate of lung metastasis were detected. The microvessel density (MVD) in tumor tissues was detected by immunohistochemical method. The expression of VEGF protein in tumor tissues was detected by Western blotting. Results The antitumor rates of ASODN, LMWH and combination therapy group were 47.34%, 27.31% and 59.03% respectively. The lung metastasis rates were 37.5%, 37.5% and 25% respectively. MVD and VEGF Compared with control group and MSODN group, the tumor inhibition rate and MVD had statistical significance (P <0.05). Conclusions VEGF-ASODN and Fumingne can down-regulate VEGF expression and anti-angiogenic effect. The combination of the two has a synergistic anti-tumor effect.