携带人Endostatin基因的腺病毒治疗胰腺癌移植瘤  

Human endostatin gene recombinant adenovirus for pancreatic carcinoma in nude mice

作　　者：吕纯业[1] 胡先贵[1] 张怡杰[1] 刘瑞[1] 金钢[1] 邵成浩[1] 

机构地区：[1]第二军医大学长海医院普外科,上海200433

出　　处：《中华胰腺病杂志》2009年第2期95-98,共4页Chinese Journal of Pancreatology

基　　金：基金项目：国家自然科学基金（30200275）;上海市青年科技启明星计划（05QMX1472）

摘　　要：目的观察携带人Endostatin基因的重组腺病毒载体Ad-hEnd对裸鼠胰腺癌移植瘤的治疗作用。方法将胰腺癌细胞株SW1990细胞皮下注射建立裸鼠移植瘤模型，随机分为Ad—hEnd组、报告基因LacZ重组腺病毒组（Ad—LacZ组）和对照组，每组8只。重组腺病毒200μl瘤内注射，隔日1次，共4次。观察移植瘤的生长情况，免疫组化染色检测血管内皮生长因子（VEGF）的表达和微血管密度（MVD），原位缺口末端标记法（TUNEL）检测肿瘤细胞凋亡。结果移植瘤成瘤率100％。治疗后4周，Ad—hEnd组、Ad-LacZ组和对照组移植瘤体积分别为（921．9±279．7）mm3、（2804．4±553．5）mm3和（3040．6±487．6）mm3；瘤重分别为（1．19±0．18）g、（2．38±0．42）g和（2．41±0．47）g；VEGF表达阳性率分别为（36．3±7．1）％、（81．2±6．6）％和（79．4±6．2）％；MVD分别为12±4、27±5和25±6；细胞凋亡率分别为（31．2±5．4）％、（9．4±4．9）％和（8．5±3．7）％。与Ad—LacZ组和对照组比较，Ad·hEnd组以上各项指标均有显著性差异（P〈0．01）；Ad—LacZ组和对照组之间的差异无统计学意义。结论重组腺病毒介导的hEndostatin基因可抑制胰腺癌的生长和血管生成，促进肿瘤细胞凋亡，可用于胰腺癌抗血管生成的基因治疗。Objective To construct a human endostatin adenovirus vector and investigate its inhibitory effect on pancreatic carcinoma in nude mice. Methods Animal model of pancreatic carcinoma bearing nude mice was established by subcutaneous injection of SW1990 cells. All mice were randomized into Ad-hEnd group, Ad-LacZ group and control group with 8 mice in each group. The endostatin gene recombinant adenovirus were intratumorally injected every two clays for 4 times. The rate of tumor growth was observed. Immunohistochemical staining was employed to investigate the expression of vascular endothelial growth factor （VEGF） and micro-vessel density （MVD）. TUNEL in situ was used to examine tumor cell apoptosis. Results The tumor formation rate was 100%. 4 weeks later, the volumes of the tumors were （921.9 ± 279.7） mm3 , （2804.4± 553.5 ）mm3 and （3040.6 ± 487.6）mm3 in Ad-hEnd group, Ad-LacZ group and control group, respectively; the weights of the tumors were （1. 19±0. 18）g, （2.38±0.42）g and （2.41 ±0.47）g, respectively; theVEGF positive rates were （36. 3 ±7. 1）%, （81.2 ±6. 6）% and （79.4 ±6. 2）%, respectively; the levels of MVD were 12 ±4, 27 ±5 and 25±6, respectively; the apoptotic rates were （31.2 ± 5.4 ） %, （ 9.4 ±4.9 ） % and （ 8.5 ± 3.7 ） %, respectively. Compared with Ad-LacZ group and control group, the parameters in Ad-hEnd group were statistically different （P 〈 0.01 ）. The difference between Ad-LacZ group and control group was not statistically different. Conclusions Human endostatin gene mediated by recombinant adenovirus could inhibit tumor growth, angiogenesis and promote cell apoptosis of pancreatic carcinoma and could be used as gene therapy for pancreatic carcinoma.

关 键 词：胰腺肿瘤 内皮抑素类 腺病毒 基因治疗 

分 类 号：R735.9[医药卫生—肿瘤]