阿司匹林对小鼠S180肉瘤生长及血管和淋巴管生成的影响  

Effects of aspirin on the growth of murine sarcoma S180 and tumor angiogenesis and lymphangiogenesis in vivo

作　　者：张晓月[1,2] 张维东[1] 王兆朋[1] 王朝霞[1] 张月英[1] 贾青[1] 

机构地区：[1]山东省医学科学院基础医学研究所病理室,济南250062 [2]济南大学山东省医学科学院医学与生命科学学院,济南250022

出　　处：《山东大学学报（医学版）》2013年第1期1-6,11,共7页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81073102;30873408);山东省自然科学基金(ZR2010HQ003;2009ZRC03044);济南市科学技术发展计划(201004012)

摘　　要：目的观察阿司匹林对小鼠S180肉瘤生长的影响,并探讨其可能的作用机制。方法昆明种小鼠40只,接种S180肉瘤细胞,随机分为荷瘤对照组、5-氟尿嘧啶(5-FU)组、阿司匹林高(250 mg/kg)、低剂量(50 mg/kg)组,描绘肿瘤体积生长曲线并计算抑瘤率;HE染色观察各组肿瘤组织病理变化;免疫组化检测各组肿瘤组织微血管密度(MVD)、淋巴管密度(LVD)、血管内皮生长因子-A(VEGF-A)、血管内皮生长因子-C(VEGF-C)的变化;Western blot检测各组肿瘤组织VEGF-A、VEGF-C的表达。结果阿司匹林高、低剂量组抑瘤率分别为45.4%和22.2%(P<0.05),与荷瘤对照组相比,5-FU组与阿司匹林高、低剂量组VEGF-A和VEGF-C的表达明显下调,LVD、MVD降低(P<0.05),阿司匹林的作用呈剂量依赖性。结论阿司匹林能抑制小鼠S180肉瘤的生长,其作用机制可能与减少VEGF-A和VEGF-C产生从而抑制肿瘤血管和淋巴管生成有关。Objective To investigate the effects of aspirin on the growth of murine sarcoma S180 and the mechanism of the inhibitory effect. Methods 40 mice were implanted with S180 cells and randomly divided into 4 groups ： the con- trol group, the 5-fluorouracil （5-FU） group, the high-dose aspirin group （250 mg/kg） and the low-dose aspirin group （50 mg/kg）. The effect of aspirin on tumor growth was observed by recording tumor growth curve and calculating the inhibition rate. Pathological changes of the tumors were observed by HE stainning. Immunohistochemistry was applied to detect microvessel density （ MVD）, lymphatic vessel density （ LVD）, the levels of vascular endothelial growth factor- A（VEGF-A） and vascular endothelial growth factor-C （VEGF-C）. Western blot was applied to detect the expressions of VEGF-A and VEGF-C. Results High-dose and low-dose aspirin had inhibitory effects on the growth of murine S180 sarcoma （P 〈 0.05）. The inhibition rates of the high-dose and low-dose aspirin groups were 45.4% and 22.2% separately （ P 〈 0.05 ）. The results of immunohistochemistry showed that the expressions of VEGF-A and VEGF-C were inhibited by aspirin. The MVD was decreased in a dose-dependent manner （P 〈 0.05）. The LVD was inhibited by5-FU and aspirin especially in the high-dose aspirin group（ P 〈 0.05 ）. Western blot results showed that the expressions of VEGF-A and VEGF-C were inhibited by aspirin. Conclusion Aspirin can inhibit the growth of murine sarcoma S180. The mechanism might be associated with the inhibitions of tumor angiogenesis and lymphangiogeresis, which are due to down-regulated expressions of VEGF-A and VEGF-C.

关 键 词：阿司匹林 血管生成 淋巴管生成 微血管密度 血管内皮生长因子 

分 类 号：R73-36[医药卫生—肿瘤]