重组人血管内皮抑素联合顺铂治疗小鼠肺转移癌实验研究  

Combination of recombinant human endostatin and DDP for treatment of murine tumor lung metastases

作　　者：杨云锋[1] 王士勇[1] 张远[1] 杜微利[1] 张晖[1] 何英[1] 武秀艳[1] 

机构地区：[1]中国医科大学附属第四医院生物治疗科,辽宁沈阳110032

出　　处：《中华肿瘤防治杂志》2011年第13期997-1001,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：教育部留学归国人员科研启动基金(2004-527)

摘　　要：目的:探讨重组人血管内皮抑素(恩度)联合顺铂抑制小鼠肺转移癌的作用和机制。方法:取H22肝癌细胞株腹水瘤反复从小鼠尾静脉注入,建立高肺转移小鼠模型,随机分为4组:生理盐水、顺铂、恩度和顺铂与恩度联合治疗组,10只/组。从尾静脉接种后第7天腹腔内给药,1次/d,连用14 d,第21天处死,解剖出小鼠肺脏,称质量,计数肺转移结节数,并对肺转移瘤组织进行免疫组化染色,检测血管内皮生长因子(VEGF)表达,计数微血管密度。结果:生理盐水组、恩度组、顺铂组和联合治疗组肺转移率分别为100%、70%、60%和40%,肺转移结节数分别为(28.6±10.2)、(20.7±5.6)、(14.3±6.4)和(8.9±3.8)个,微血管密度计数为(31.4±3.1)、(24.6±5.9)、(21.2±4.7)和(15.2±3.1),各治疗组结果与生理盐水组比较差异均有统计学意义(P<0.05),联合组与顺铂组或恩度组比较也具有差异(P<0.05)。生理盐水组肺转移瘤组织的VEGF表达明显高于各治疗组(P<0.05)。结论:恩度单用或联合顺铂均能显著抑制H22肝癌肺转移组织的血管生成,降低了肺转移。OBJECTIVE： To investigate the inhibitory effects of recombinant human endostatin with DDP on the lung metastatic tumor of mice. METHODS： To obtain the highly pulmonary metastatic Kunming mice injected with H22 hepatic cells from tail vein. Forty highly pulmonary metastatic mice were divided into four groups （n=10） to receive the injection of physiological saline, endostatin, DDP and endostatin plus DDP, receptively for fourteen days-seven days after the inoculation. On the 21st day, all the mice were scarified and their lungs were weighted, the lung metastatic foci of implanted tumors were calculated with the microscope. Immunohistochemistry was used to determine the microvessel density （MVD） and the expression of vascular endothelial growth factor （VEGF）. RESULTS： The pulmonary metastatic rate of tumor in physiological saline group, DDP group, endostatin group and combination group were 100%, 70%, 60% and 40%, respectively, the number of metastatic tuber were 28.6±10.2, 20.7±5.6, 14.3±6.4 and 8.9±3.8, and the MVD were 31.4±3.1, 24.6±5.9, 21.2±4.7 and 15.2±3.1. The pulmonary metastasis rate, the number of metastasis tuber and the MVD were significantly different between the physiological saline group and three treatment groups （P〈0.05）, and it was also observed between the combination group and the DDP group or the endostatin group （P〈0.05）. Compared with physiological saline group, the expression of VEGF in three treatment groups was significantly inhibited （P〈0.05）. CONCLUSION： Endostatin in combination with DDP can potently inhibit the angiogenesis and lung metastasis of mouse with inoculation of H22 hepatoma cells.

关 键 词：重组人血管内皮抑素 肺转移 血管内皮生长因子 微血管密度 肝肿瘤 实验性 

分 类 号：R734.2[医药卫生—肿瘤] R73-37[医药卫生—临床医学]