rmh-TNF协同顺铂抗小鼠Lewis肺癌血管生成的作用  

Recombinant mutant human tumor necrosis factor enhances anti-angiogenesis effect of cisplatin on Lewis lung carcinoma in mice

作　　者：魏素菊[1] 尤江莲[1] 韩文峰[1] 刘义冰[1] 

机构地区：[1]河北医科大学附属第四医院肿瘤内科,石家庄050011

出　　处：《中国肿瘤生物治疗杂志》2008年第3期264-268,共5页Chinese Journal of Cancer Biotherapy

基　　金：河北省科技攻关计划(No.072761147)~~

摘　　要：目的:观察重组改构人肿瘤坏死因子(recombinant mutant human tumor necrosis factor,rmh-TNF)协同顺铂(cispla- tin,又称DDP)抗小鼠Lewis肺癌血管生成的作用。方法:建立C57BL/6小鼠Lewis肺癌模型,随机分为4个治疗组:生理盐水对照组、rmh-TNF(150万U/kg)组、DDP(6.15 mg/kg)组、联合用药组(DDP+rmh-TNF)。接种肿瘤细胞后12 d开始瘤内注射药物3 d,RT-PCR法测定瘤组织中HIF-1α的表达,免疫组化法检测肿瘤组织血管内皮生长因子(vascular endothelial growth fector,VEGF)、激酶结构域受体(kinase domain region receptor,KDR)、微血管密度(microvascular density receptor,MVD)的表达,流式细胞术测定基质金属蛋白酶2(matrix metalloproteinase-2,MMP-2)的表达。结果:对照组、rmh-TNF组、DDP组和联合用药组小鼠肿瘤组织中的MVD数分别为(24.76±1.28)、(18.95±1.22)、(19.53±1.15)、(10.43±1.05),两单药组的MVD数明显低于对照组(P<0.05);联合用药组低于两单药组(P<0.05)。HIF-1αmRNA相对表达水平分别为(0.171±0.004)、(0.138±0.006)、(0.134±0.006)、(0.095±0.006),两单药组较对照组明显下降(P<0.05),联合用药组明显低于两单药组(P<0.05)。肿瘤组织中MMP-2蛋白的荧光指数FI值依次为(1.000±0.000)、(0.875±0.020)、(0.848±0.127)、(0.545±0.107),单药组的MMP-2蛋白的(FI)值较对照组明显下降(P<0.05),联合用药组明显低于两单药组(P<0.05)。单药组VEGF、KDR表达均明显低于对照组(P<0.05),联合用药组的表达均低于各单药组(P<0.05)。结论:rmh-TNF能够增强DDP抗小鼠Lewis肺癌血管生成的作用。Objective： To observe the role of rmh-TNF in enhancing the anti-angiogenesis effect of cisplatin on Lewis lung carcinoma in the mice. Methods： Lewis lung carcinoma model was established in C57BL/6 mice. Sixty model mice were randomly divided into 4 groups： control group, rmh-TNF group（ 1 500 000 U/kg）, cisplatin group（6.15 mg/kg）, and rmh-TNF plus cisplatin group. Twelve days after implantation of cancer cells, different drugs were injected intratumorally for 3 d. The expression of hypoxia inducible factor-1α（HIF-1α） gene in the tumor was identified by RT-PCR. Immunohistochemistry （IHC） image analysis was performed to determine the vascular endothelial growth factor （VEGF） and kinase domain region receptor （KDR） expression and the microvessel density（MVD）. Expression of matrix metalloproteinase-2（ MMP-2 ） was detected by flow cytometry. Results： The MVD values in the control group, the rmh-TNF group, the DDP group and the combination group were （24.76 ± 1.28）, （ 18.95 ± 1.22）, （ 19.53 ± 1.15）, （ 10.43 ± 1.05）, respectively, with those of the rmh-TNF and DDP groups significantly lower than that of the control group and higher than that of the combination group （ all P 〈 0.05 ）. The relative levels of HIF-1α mRNA in the control group, rmh-TNF group, DDP group and the combination group were （0. 171 ± 0. 004 ）, （0. 138 ±0. 006 ）, （0. 134 ± 0. 006 ）, （0. 095 ± 0. 006）, respectively, with the levels in the single drug groups significantly lower than that in the control group （ P 〈 0.05 ） and higher than that of the combination group （ P 〈 0.05 ）. The relative levels of MMP-2 in the control group, rmh-TNF group, DDP group and combination group were （ 1. 000±0. 000）, （0. 875 ± 0. 020）, （0. 848 ±0.127 ）, and （0. 545 ± 0. 107 ）, respectively, with those of the single drug groups significantly lower than that of the control group and higher than that of the combination group （ respectively P 〈 0.05 �

关 键 词：重组改构人肿瘤坏死因子 顺铂 LEWIS肺癌 抗血管生成 协同作用 

分 类 号：R734.2[医药卫生—肿瘤] R730.54[医药卫生—临床医学]