陈雨薇;张虹;杨超;强娟;

• 1:天津医科大学
• 2:天津市中心妇产科医院

摘要(Abstract)：

目的:探讨转染Smac基因对卵巢癌SKOV3/DDP裸鼠移植瘤顺铂敏感性及微血管生成的影响。方法:建立卵巢癌SKOV3/DDP裸鼠移植瘤模型,随机分为5组,分别给予不同药物干预:(1)对照组:移植瘤内注射生理盐水;(2)DDP组:腹腔内注射顺铂;(3)空质粒+DDP组:移植瘤内注射空质粒,24h后腹腔内注射顺铂;(4)Smac组:移植瘤内注射Smac重组质粒;(5)Smac+DDP组:移植瘤内注射Smac重组质粒,24h后腹腔内注射顺铂。顺铂浓度为0.5mg/m1,给药剂量按3mg/kg计算。观察各组裸鼠移植瘤体积变化,计算抑瘤率。TUNEL法检测移植瘤组织标本的凋亡指数,免疫组化法检测CD34并计算微血管密度(MVD)。结果:Smac+DDP组的移植瘤体积最小,平均抑瘤率72.94%,与其他组比较差异有统计学意义(P<0.05)。对照组、DDP组、空质粒+DDP组、Smac组、Smac+DDP组的凋亡指数分别为(19.90±3.18)%,(21.82±4.40)%,(22.64±3.81)%,(30.23±4.06)%,(48.59±4.47)%,MVD计数分别为(24.8±5.36),(21.2±3.11),(19.8±3.70),(14.4±3.85),(11.6±2.70)。其中,Smac+DDP组的凋亡指数最高,MVD最低,与其他组比较差异有统计学意义(P<0.05)。结论:Smac基因转染可增强卵巢癌耐药移植瘤对顺铂的敏感性,同时减少微血管生成。

关键词(KeyWords)： 卵巢癌;顺铂耐药;裸鼠;Smac;凋亡

Abstract:

Keywords:

基金项目(Foundation): 天津卫生局科技基金重点项目(其他)

作者(Authors): 陈雨薇;张虹;杨超;强娟;

DOI: 10.13283/j.cnki.xdfckjz.2016.02.001

参考文献(References)：

• [1]曹泽毅.中华妇产科学(临床版)[M].第2版.北京:人民卫生出版社,2010:640-650
• [2]Mansouri A,Zhang Q,Ridgway LD,et al.Cisplatin resistance in an ovarian carcinoma is associated with a defect in programmed cell death control through XIAP regulation[J].Oncol Res,2003,13(6-10):399-404
• [3]Martinez-Ruiz G,Maldc Inado V,Ceballos-Cancino G,et al.Role of Smac/DIABLO in cancer progression[J].J Exp Clin Cancer Res,2008,27(1):48-55
• [4]Yin A,Jiang Y,Zhang X,et al.Transfection of PDCD5sensitizes colorectal cancer cells to cisplatin-induced apoptosis invitro and in vivo[J].Eur J Pharmacol,2010,649(1-3):120-126
• [5]Syrios J,Banerjee S,Kaye SB.Advanced epithelial ovarian cancer:from Sstandard chemotherapy to promising molecular pathway targets——where are we now?[J].Anticancer Res,2014,34(5):2069-2077
• [6]Davis A,Tinker AV,Friedlander M.Platinum resistant"ovarian cancer:what is it,who to treat and how to measure benefit?[J].Gynecol Oncol,2014,133(3):624-631
• [7]Hu S,Yang X.Cellular inhibitor of apoptosis 1 and 2 are ubiquitin ligases for the apoptosis inducer Smac/DIABLO[J].J Bio Chem,2003,278(12):10055-10060
• [8]李丹,张虹,曲芃芃.Smac基因转染对卵巢上皮性癌细胞凋亡的影响[J].中华妇产科杂志,2010(3):12-14
• [9]强娟,张虹.Smac和XIAP与卵巢癌细胞耐药及凋亡关系的研究[J].中华临床医师杂志(电子版),2014(22):4033-4039
• [10]Pan QW,Zhong SY,Liu BS,et al.Enhanced sensitivity of hepatocellular carcinoma cells to chemotherapy with a Smac-armed oncolytic adenovirus[J].Acta Pharmacol Sin,2007,28(12):1996-2004
• [11]Boehm T,Folkman J,Browder T,et al.Antiangiogenic therapy ofexperimental cancel"does not induce acquired drug resistance[J].Nature,1997,390(6658):404-407
• [12]Hollingsworth HC,Kohn EC,Steinberg SM,et al.Tumor angiogenesis in advanced stage ovarian carcinoma[J].Am J Pathol,1995,147(1):33-41
• [13]Raspollini MR,Amunni G,Villanucci A,et al.Prognostic significance of microvessei density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma[J].Int J Gynecol Cancer,2004,14(5):815-823