Fat-1基因对人子宫内膜癌Ishikawa细胞体内生长抑制作用Expression of Fat-1 gene inhibits the growth of human endometrial cancer Ishikawa cells in vivo
梁升;陆晓媛;
摘要(Abstract):
目的:探究腺病毒介导的Fat-1基因(Ad-GFP-Fat-1)对人子宫内膜癌Ishikawa细胞体内抑制效应及其潜在的分子机制。方法:体外培养人子宫内膜癌Ishikawa细胞,接种于裸鼠右前肢腋部,建立人子宫内膜癌裸鼠皮下移植瘤模型。将成瘤后裸鼠随机分成3组:Ad-GFP-Fat-1实验组、Ad-GFP空载体组、PBS对照组,分别对裸鼠进行皮下移植瘤注射治疗。观察并测量瘤体体积。RT-PCR检测Fat-1基因表达,TUNEL+DAPI染色法检测移植瘤组织凋亡,免疫组化SP法和Western blot检测瘤体内半胱氨酸蛋白酶(Caspase)-3的表达情况。结果:Fat-1基因在Ad-GFP-Fat-1组移植瘤组织中有效异源表达。Ad-GFP-Fat-1组裸鼠移植瘤的体积和重量明显小于Ad-GFP组和PBS组(瘤体比较:P<0.05,瘤重比较:P<0.05)。Ad-GFP-Fat-1组的凋亡指数明显高于Ad-GFP组和PBS组(P<0.05)。Ad-GFP-Fat-1可明显上调Caspase-3表达。Ad-GFP-Fat-1主要通过增加活化的Caspase-3(Cleaved Caspase-3)上调Caspase-3表达。结论:Ad-GFP-Fat-1表达对人子宫内膜癌裸鼠皮下移植瘤有抑制作用,其机制可能与Fat-1基因上调Cleaved Caspase-3表达诱导细胞凋亡有关。
关键词(KeyWords): 腺病毒载体;裸鼠;Fat-1基因;Caspase-3;子宫内膜癌
基金项目(Foundation): 江苏省卫生厅医学科研项目(No:H201428)
作者(Authors): 梁升;陆晓媛;
DOI: 10.13283/j.cnki.xdfckjz.2017.05.004
参考文献(References):
- [1]Jemal A,Bray F,Center MM,et al.Global cancer statistics[J].CA Cancer J Clin,2011,61(2):69-90
- [2]Zyla MM,Kostrzewa M,Litwinska E,et al.The role of angiogenic factors in endometrial cancer[J].Prz Menopauzalny,2014,13(2):122-126
- [3]Gerber M.Backgroud reviewpaper on total fat,fatty acid intakeand cancers[J].Ann Nutr Metab,2009,55(1-3):140-161
- [4]Zhang Y,Xu F,Liang H,et al.Exenatide inhibits the growth of endometrial cancer Ishikawa xenografts in nude mice[J].Oncol Rep,2016,35(3):1340-1348
- [5]Wu JQ,Zhao WH,Li Y,et al.Adeno-associated virus mediated gene transfer into lung cancer cells promoting CD40ligand-based immunotherapy[J].Virol,2007,368(2):309-316
- [6]朱永进,朱奇.Image-Pro Plus计数阳性细胞进阶教程[J].医药前沿,2012,2(8):129-130
- [7]Zhao J,Lyu C,Gao J,et al.Dietary fat intake and endometrial cancer risk:A dose response meta-analysis[J].Med,2016,95:e4121
- [8]Lu XY.Effects of polyunsaturated fatty acids on endometrial carcinoma Ishikawa cells[J].Eur Review Med Pharmacol Sci,2014,18(21):3311-3314
- [9]Xia SH,Wang J.Decreased n-6/n-3 fatty acid ratio reduces the invasive potential of human lung cancer cells by downregulation of cell adhesion/invasion-related genes[J].Carciongenesis,2005,26(4):779-784
- [10]Kang ZB,Ge Y,Chen Z,et al.Adenoviral gene transfer of Caenorhabditis elegans n-3 fatty acid desaturase optimizes fatty acid composition in mammalian cells[J].Proc Natl Acad Sei USA,2001,98(7):4050-4054
- [11]Budihardjo I,Oliver H,Lutter M,et al.Biochemical pathways of caspase activation during apoptosis[J].Annau Rev Cell Dev Biol,1999,15:269-290
- [12]Zhu AK,Zhou H,Xia JZ,et al.ZiyuglycosideⅡ-induced apoptosis in human gastric carcinoma BGC-823 cellsby regulating Bax/Bcl-2 expression an activating caspase-3pathway[J].Braz J Med Biol Res,2013,46(8):670-675
- [13]戴莉,冯茂辉,杨炯,等.白藜芦醇对肺腺癌A549细胞裸鼠移植瘤的抑制作用[J].中华实验外科杂志,2015,32(12):3074-3077
- [14]Nie D,Wang Z,Zhang Y,et al.Fat-1 gene inhibits human oral squamous carcinoma cell proliferation through downregulation ofβ-catenin signaling pathways[J].Exp Ther Med,2016,11(1):191-196