放疗对lewis肺癌荷瘤小鼠MMP、VEGF、MVD的影响  

Effect of Irradiation on Matrix Metalloproteinases,Vascular Endothelial Growth Factor and Microvessel Density of Mice Bearing Lewis Lung Cancer

作　　者：艾平[1] 任志刚[2] 王辛[3] 王世超[4] 李平[1] 

机构地区：[1]四川大学华西医院肿瘤中心头颈乳腺肿瘤科,成都610041 [2]复旦大学附属肿瘤医院放疗科 [3]四川大学华西医院肿瘤中心腹部肿瘤科 [4]四川大学华西医院肿瘤放射治疗中心

出　　处：《四川大学学报（医学版）》2009年第4期632-635,共4页Journal of Sichuan University(Medical Sciences)

摘　　要：目的建立lewis肺癌荷瘤小鼠动物模型,研究局部放疗对与肿瘤生长、转移密切相关的基质金属蛋白酶(MMPs)、血管内皮生长因子(VEGF)和微血管密度(MVD)表达的影响。方法建立负载lewis肺癌细胞的C57BL/6荷瘤小鼠动物模型,随机分为放疗组和未放疗组。当肿瘤细胞接种后14d,肿瘤体积增至190mm3左右时,放疗组应用医用直线加速器6MV-X射线对原发肿瘤分次照射,5Gy/次,隔日1次,共20Gy/4次。当放疗结束后第8d(即接种后28d),小鼠开始出现呼吸困难时,同时处死放疗组、未放疗组小鼠。解剖小鼠取原发瘤、癌旁正常组织。免疫组化法检测原发瘤及癌旁正常组织中基质金属蛋白酶2(MMP2)、基质金属蛋白酶9(MMP9)、原发瘤中VEGF、MVD的表达。结果肿瘤组织中MMP2、MMP9表达高于癌旁正常组织(P<0.05);放疗组肿瘤组织中MMP2、MMP9、VEGF、MVD较未放疗组表达增强(P<0.05),而癌旁正常组织中MMP2、MMP9无明显变化。结论放疗增强了lewis肺癌荷瘤小鼠肿瘤组织中MMP2、MMP9、VEGF、MVD的表达,为临床联合运用放疗与MMP抑制剂以及其它抗血管生成治疗,提高肿瘤治疗疗效提供了实验依据。Objective To investigate the effect of irradiation on matrix metalloproteinases （MMPs）,vascular endothelial growth factor （VEGF）and microvessel density（MVD）, which influence on tumor growth and metastases of mice bearing Lewis lung cancer（LLC）. Methods C57BL/6 mice bearing LLC were randomized into two groups to receive radiation and noradiation,respectively. When tumor reached about 190 mma in volume on the fourteenth day after inoculation, the radiation group was irradiated to the primary tumor （6 MV-X, 5 Gy/day, d14,16,18,20）. On the eighth day after irradiation, animals were killed to examine primary tumors, normal tissue near tumors. MMP-2, MMP-9, VEGF and MVD were checked by immunohistochemical means. Results Immunohistochemical examination demonstrated an increased expression of MMP2, MMP9, VEGF and MVD in the tumor tissue of the radiation group（P〈0.05）. Additionally, the expression levels of MMP2 and MMP9 in the tumor tissue were higher than those in the normal tissue near tumor（P〈0. 05）. Conclusion This study showed that irradiation might increased MMP2,MMP9,VEGF and MVD expression in the tumor tissue of mice bearing Lewis lung cancer. Our finding supports a potential way to overcome tumor metastasis induced by radiation if MMP inhibitor and antivaseularization are combined to irradiation clinically.

关 键 词：放射治疗 基质金属蛋白酶 血管内皮生长因子 微血管密度 LEWIS肺癌 小鼠模型 

分 类 号：R734.2[医药卫生—肿瘤]