肝动脉栓塞化疗联合恩度治疗对兔VX2肝移植瘤生长及血管生成的影响  

Effects of TACE combined with Endostar on angiogenesis and the growth of transplanted VX2 hepatic tumor in rabbits

作　　者：谢斌[1] 位晓丹[1] 高志芹[1] 吴潼[1] 石剑飞[1] 蹇兆成[2] 孙业全[2] 王滨[2] 

机构地区：[1]潍坊医学院细胞生物学教研室,山东潍坊261053 [2]潍坊医学院附属医院影像中心,山东潍坊261053

出　　处：《中国药理学通报》2011年第6期844-848,共5页Chinese Pharmacological Bulletin

基　　金：山东省科技发展计划资助项目(No2007GG30002032)

摘　　要：目的探讨肝动脉栓塞化疗(TACE)恩度联合应用对兔VX2肝移植瘤生长及血管生成的影响。方法建立兔VX2肝移植瘤模型,并随机分为对照组、TACE组和抗血管生成组(TACE+恩度),二维超声监测肿瘤的生长情况,HE染色、免疫组化法检测CD31、PCNA的表达,Western bolt检测血管内皮生长因子(vascular endothelial growth factor,VEGF)表达。对微血管密度(microvessel density,MVD)、VEGF与肿瘤体积生长率(volume growth rate,VGR)间进行相关性分析。结果治疗后7、14 d,抗血管生成组肿瘤体积生长率与对照组比较,差异具有统计学意义(P<0.05)。治疗后14 d,抗血管生成组细胞增殖指数(proliferation index,PI)(62.83±7.82)明显低于TACE组(85.36±10.37)和对照组(82.67±11.25)(P<0.05);抗血管生成组MVD值(31.55±6.71)最低,与其余两组相比差异具有统计学意义(P<0.05)。TACE组VEGF的相对表达水平(1.29±0.11)高于抗血管生成组(0.60±0.05)和对照组(0.85±0.06),差异具有统计学意义(P<0.05),抗血管生成组与对照组相比,差异也具有统计学意义(P<0.05)。各组肿瘤VEGF表达与MVD、VGR均呈正相关性(r=0.933,r=0.563,P<0.05)。结论 TACE与恩度联合应用与单纯应用TACE相比可明显抑制兔VX2肝移植瘤的生长及肝癌组织细胞增殖,下调VEGF的表达,抑制肿瘤的血管生成。Aim To investigate the effects of TACE combined with Endostar on angiogenesis and the growth of transplanted VX2 hepatic tumor in rabbits.Methods Model of transplanted VX2 hepatic tumor in rabbits was established.The model rabbits were divided into TACE,anti-angiogenesis and control groups.Planar sonography was applied to detect the size and growth of the tumor.14 days after TACE treatment,the expressions of PCNA and CD31 were detected by immunohis-tochemistry.The expression of VEGF protein was observed by Western blot.The correlation between the expressions of microvessel density（MVD）,VEGF and tumor volume growth rate（VGR）was analyzed.Results 7 days and 14 days after treatment,the average tumor VGR was significantly lower in anti-angiogenesis group than in TACE group and control group（P0.05）.14 days after trantment the proliferation index and MVD were significantly lower in anti-angiogenesis group than in TACE group and control group（62.83±7.82 vs 85.36±10.37 vs 82.67±11.25,P0.05; 31.55±6.71 vs 53.18±7.58 vs 56.53±10.47,P0.05）.The expression levels of VEGF was significantly higher in TACE group（1.29±0.11）than in anti-angiogenesis group（0.60±0.05）and control group（0.85±0.06）（P0.05）.VEGF expression in each group was positively correlated to MVD and VGR（r=0.933,r=0.563 both P0.05）.Conclusions Compared with single TACE,TACE combined with endostar can significantly inhibit the growth and the proliferation of transplanted VX2 hepatic tumor in rabbits,decline of the expression of VEGF protein,suppress the tumor angiogenesis.

关 键 词：血管生成抑制剂 肝动脉栓塞化疗 PCNA Westernbolt 微血管密度 血管内皮生长因子 

分 类 号：R-332[医药卫生] R329.24