抑制VEGF-B表达对人绒毛膜癌裸鼠移植瘤影响的研究The effects of VEGF-B by inhibiting its expression in human chorionic carcinoma transplantation tumor in nude mouse
彭金萍;蔡净亭;刘惠宁;胡萃;谭倩霞;
摘要(Abstract)：
目的:研究RNA干扰下调血管内皮生长因子-B(VEGF-B)表达对人绒毛膜癌裸鼠移植瘤生长、侵袭转移及血管生成的影响。方法:将构建的含VEGF-B shRNA的质粒转染人绒毛膜癌细胞JEG-3,建立裸鼠皮下移植瘤模型。观察shRNA干扰VEGF-B表达对JEG-3裸鼠移植瘤生长及侵袭转移能力的影响,并采用免疫组化技术检测移植瘤组织中VEGF-B的表达变化及其所含CD34标记的肿瘤微血管密度(MVD)的差异。结果:(1)抑制VEGF-B表达可减小裸鼠皮下肿瘤大小(P<0.05),并降低肿瘤细胞肺转移的发生率(P<0.05);(2)免疫组化结果提示,VEGF-B shRNA转染组移植瘤中VEGF-B表达及MVD均低于空白对照组和阴性对照组(P<0.05);(3)相关性分析显示,VEGF-B蛋白表达水平与绒毛膜癌MVD高低成正相关。结论:VEGF-B基因在绒毛膜癌的体内生长、侵袭转移中起重要作用,shRNA下调其表达能抑制绒毛膜癌细胞的体内生长、侵袭转移,可能与其调控瘤组织内的微血管形成有关。
关键词(KeyWords)： RNA干扰;VEGF-B;人绒毛膜癌;侵袭转移;血管生成
基金项目(Foundation): 国家自然科学基金项目资助(No:81472434)
作者(Authors): 彭金萍;蔡净亭;刘惠宁;胡萃;谭倩霞;
DOI: 10.13283/j.cnki.xdfckjz.2015.02.007
参考文献(References)：
- [1]Liu HN,Cai JT,Keren H.Metastasis gene expression analyses of choriocarcinoma and the effect of silencing metastasis-associated genes on metastatic ability of choriocarcinoma cells[J].Eur J Gynaecol Oncol,2011,32(3):264-268
- [2]胡惠,刘惠宁,何可人,等.血管内皮生长因子B在绒毛膜癌侵袭中的作用[J].中华妇产科杂志,2010,45(2):148-150
- [3]许良中,杨文涛.免疫组织化学反应结果的判断标准[J].中国癌症杂志,1996(4):229-231
- [4]Weidner N.Chapter 14,Measuring intratumoral microvessel density[J].Methods Enzymol,2008,444:305-323
- [5]Carrillo De Santa Pau E,Arias FC,et al.Prognostic significance of the expression of vascular endothelial growth factors A,B,C,and D and their receptors R1,R2,and R3 in patients with nonsmall cell lung cancer[J].Cancer,2009,115(8):1701-1712
- [6]Mylona E,Alexandrou P,Giannopoulou I,et al.The prognostic value of vascular endothelial growth factors(VEGFs)-A and-B and their receptor,VEGFR-1,in invasive breast carcinoma[J].Gynecol Oncol,2007,104(3):557-563
- [7]Kawakami M,Furuhata T,Kimura Y,et al.Expression analysis of vascular endothelial growth factors and their relationships to lymph node metastasis in human colorectal cancer[J].J Exp Clin Cancer Res,2003,22(2):229-237
- [8]Bry M,Kivela R,leppanen VM,et al.Vascular endothelial growth factor-B in physiology and disease[J].Physiol Rev,2014,94(3):779-794
- [9]Lautenschlaeger T,George T,Klimo Wicz A C,et al.Bladder preservation therapy for muscle-invading bladder cancers on Radiation Therapy Oncology Group trials 8802,8903,9506,and 9706:vascular endothelial growth factor B overexpression predicts for increased distant metastasis and shorter survival[J].Oncol,2013,18(6):685-686
- [10]Fischer C,Mazzone M,Jonckx B,et al.FLT1 and its ligands VEGFB and Pl GF:drug targets for anti-angiogenic therapy?[J].Nat Rev Cancer,2008,8(12):942-956
- [11]Shintani S,Li C,Ishikawa T,et al.Expression of vascular endothelial growth factor A,B,C,and D in oral squamous cell carcinoma[J].Oral Oncol,2004,40(1):13-20
- [12]Albrecht I,Kopfstein L,Strittmatter K,et al.Suppressive effects of vascular endothelial growth factor-B on tumor growth in a mouse model of pancreatic neuroendocrine tumorigenesis[J].PLo S One,2010,5(11):e14109
- [13]Bhardwaj S,Roy H,Heikura T,et al.VEGF-A,VEGF-D and VEGF-D(Delta NDelta C)induced intimal hyperplasia in carotid arteries[J].Eur J Clin Invest,2005,35(11):669-676
- [14]Bhardwaj S,Roy H,Gruchala M,et al.Angiogenic responses of vascular endothelial growth factors in periadventitial tissue[J].Hum Gene Ther,2003,14(15):1451-1462
- [15]Sands M,Howell K,Costello CM,et al.Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung[J].Respir Res,2011,12:17
- [16]Lahteenvuo JE,Lahteenvuo MT,Kivela A,et al.Vascular endothelial growth factor-B induces myocardium-specific angiogenesis and arteriogenesis via vascular endothelial growth factor receptor-1-and neuropilin receptor-1-dependent mechanisms[J].Circulation,2009,119(6):845-856
- [17]Silvestre JS,Tamarat R,Ebrahimian TG,et al.Vascular endothelial growth factor-B promotes in vivo angiogenesis[J].Circ Res,2003,93(2):114-123