重组人血管内皮抑素联合NP方案对人乳腺癌裸鼠移植瘤作用的实验研究

Experimental study of recombinant human endostatin combined with NVB-Cisplatin on human breast cancer xenografts in nude mice

目的:探讨重组人血管内皮抑素(Recombinanthumanendostatin,rh-ES)联合长春瑞滨+顺铂(NP方案)化疗对人乳腺癌裸鼠移植瘤的肿瘤生长及新生血管生成的抑制作用。方法:将40只荷瘤裸鼠随机分成NP方案组(A组)、rh-ES组(B组)、联合用药组(C组)和空白对照组(D组),每组10只。A组给予NP方案化疗1周期,B组给予rh-ES 2周期,C组给予rh-ES两周期加NP方案1周期,D组给予等剂量生理盐水。其中,rh-ES连续用药14 d为1周期,间隔7 d后重复1周期。计算各组抑瘤率,绘制肿瘤生长曲线。肿瘤组织进行免疫组化法染色,测各组血管内皮生长因子(Vascular endothelial growth factor,VEGF)及微血管密度(Microvascular density,MVD)的表达。结果:A、B、C 3组抑瘤率分别为61.80%、64.79%、88.95%,C组抑瘤率明显高于其它两组。C组与A、D两组比较VEGF表达,具有显著的统计学差异(P值均为0.001)。C组与A、B、D 3组比较MVD,P值分别为0.000,0.006和0.000,均具有统计学意义。结论:rh-ES联合NP方案化疗能明显抑制人乳腺癌裸鼠移植瘤生长及新生血管生成,且两者联用具有协同作用。

Objective：To evaluate the inhibitory effect of recombinant human endostatin（rh-ES） combined with NP treatment on tumor growth and antiagiogenesis in nude mice after xenograft of MCF-7 cell line.Methods：40 nude mice models with human breast carcinoma were divided into group NVB-Cisplatin（group A）,group rh-ES（group B）,group NVB-Cisplatin ＋ rh-ES（group C）and control group（group D）,each group had 10 nude mice.Group A was given NP treatment one cycle.Group B was given rh-Endostatin two cycles.Group C was given NP treatment one cycle combined with rh-Endostatin two cycles.Group D was given normal saline solution respectively.Rh-Endostatin was used two cycles,each cycle for 14 days,two cycles interval 7 days.Tumor inhibition rate（TIR）and growth curve of each group was calculated and plotted.The vascular endothelial growth factor（VEGF）and microvascular density（MVD）expression were detected by immunohistochemistry.Results：TIR of A,B and C groups were 61.80%,64.79% and 88.95%.The TIR of group C was obviously higher than other two groups.Compared with VEGF expression,group C was significantly lower than group A and group D（both P were 0.001）.Compared with MVD,group C was significantly lower than other three groups.Conclusion：Rh-Endostatin combined NP treatment have synergistic effect,they can obviously inhibit tumor growth and angiogenesis.