利用IGF-1基因敲除鼠乳腺癌模型研究IGF-1对血管生成的影响  

Study of Influence of IGF-1 on Angiogenesis by Using IGF-1 Deficient Mice Breast Cancer Models

作　　者：任玉萍[1] 叶子荣[1] 唐泓波[1] 张军[1] 张珊[1] 陈国庆[1] 吴毅平[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院整形外科,武汉430030

出　　处：《中国普外基础与临床杂志》2008年第11期820-824,共5页Chinese Journal of Bases and Clinics In General Surgery

基　　金：国家自然科学基金资助项目(编号:30271280)~~

摘　　要：目的探讨在低血清胰岛素样生长因子-1(IGF-1)水平与正常IGF-1水平的小鼠乳腺癌模型中应用血管生长抑制剂人参皂甙(GS)Rg3后,IGF-1对血管生成的影响。方法应用7,12-二甲基苯蒽(DMBA)诱导肝脏特异性IGF-1基因敲除鼠(LID鼠)及对照鼠建立原发乳腺癌模型,应用GSRg3进行干预治疗,利用免疫组化法检测乳腺癌组织中血管内皮生长因子(VEGF)和Ⅷ因子相关抗原(F8-RAg)表达水平,同时利用基因芯片技术检测小鼠乳腺癌及正常乳腺组织中相关基因的表达情况。结果LID鼠乳腺癌的发生率低于对照鼠(P<0.05);LID鼠乳腺癌组织中VEGF表达水平与微血管密度均低于对照组(P<0.05)。LID鼠乳腺癌组织中IGF-1、成纤维细胞生长因子(FGF)-1、肝细胞生长因子(HGF)和转化生长因子(TGF)-β1基因较对照组上调,成纤维细胞生长因子受体(FGFR)-2、血小板源性生长因子(PDGF)-A和PDGF-B基因较对照组下调;应用GSRg3后,LID鼠乳腺癌组织中VEGFa、表皮生长因子(EGF)、表皮生长因子受体(EGFR)、PDGF-A和FGFR-2基因较对照组上调,而IGF-1和TGF-β1基因较对照组下调。结论IGF-1促进小鼠乳腺癌的发生、发展,且与血管生长密切相关。血管生长抑制剂可能通过IGF-1及TGF-β1发挥抗肿瘤作用。Objective To determine the effect of insulin-like growth factor-1 （IGF-1） on angiogenesis in mouse breast cancer model of lower and normal serum IGF-1 levels after using angiogenesis inhibitor ginsenoside Rg3 （GS Rg3）. Methods The breast cancer models were established in control mice and liver specific IGF-1 deficient （IAD） mice by feeding DMBA and were treated with GS Rg3. Vascular endothelial growth factor （VEGF） and F8-RAg were detected by immunohistoehemical method in breast cancer tissues. IGF-1 gene and angiogenesis relating genes were detected by gene chip in breast cancer and normal breast tissue. Results The incidence rate of breast cancer in LID mice was tower than that in control mice （P〈0.05）. VEGF expression and microvessel density of LID mice were lower than those in control mice （P〈0.05）. Compared to the control mice, IGF-1, FGF-1, TGF-β1 and HGF genes were increased, and FGFR-2, PDGF-A and PDGF-B genes were decreased in breast cancer of LID mice. After GS Rg3 treatment, VEGFa, EGF, EGFR, PDGF-A and FGFR-2 genes were increased, IGF1 and TGF-β1 genes were decreased in breast cancer of LID mice compared with the control mice. Conclusion IGF-1 may be involved in mouse breast cancer progression and associated with the growth of blood vessels. Angiogenesis inhibitor may play an antitumor role by IGF-1 and TGF-β1.

关 键 词：胰岛素样生长因子-1基因敲除鼠 血管内皮生长因子 乳腺癌 人参皂甙 基因芯片 

分 类 号：R737.9[医药卫生—肿瘤]