苏拉明联合阿霉素对肺腺癌小鼠移植瘤组织中HIF-1α和VEGF表达的调控及意义  

The effect of suramin in combination with adriamycin on HIF-1α and VEGF expressions in mice transplanted with lung adenocarcinoma

作　　者：欧立文[1] 罗云海[1] 贺兼斌[2] 张平[2] 

机构地区：[1]湘南学院附属医院呼吸内科,湖南郴州423000 [2]南华大学护理学院临床护理教研室

出　　处：《中国医师杂志》2006年第11期1462-1464,共3页Journal of Chinese Physician

基　　金：湖南省卫生厅科研课题资助项目(C2005033)

摘　　要：目的研究苏拉明联合阿霉素对肺腺癌小鼠移植瘤组织中缺氧诱导因子-1α(H IF-1α)和血管内皮细胞生长因子(VEGF)表达的调控及对移植瘤增殖的影响。方法复制肺腺癌LA795细胞的T739小鼠异体移植瘤模型。40只实验小鼠皮下移植处均成瘤,接种后4d随机分为4组,10只/组。对照组:生理盐水0.2 m l/只,于接种后第4天开始腹腔注射,1次/d,共16次;阿霉素组:阿霉素(2 mg.kg-1.d-1)溶于0.2 m l生理盐水中,于接种后第4,11,18天各腹腔注射1次;苏拉明组:苏拉明(10 mg.kg-1.d-1)溶于0.2 m l生理盐水中,余同对照组;联合组(阿霉素+苏拉明):按阿霉素组和苏拉明组用药。肿瘤接种后24 d,测量小鼠皮下肿瘤最大长径(a)和横径(b),计算肿瘤体积;处死后剥离皮下肿瘤称湿重,收集肿瘤标本固定,用免疫组化和图像分析系统定量检测肿瘤组织H IF-1α、VEGF、微血管密度(MVD)和增殖细胞核抗原(PCNA)的表达。结果各治疗组肿瘤体积和湿重均低于对照组,其中以联合组最低,差异有统计学意义。苏拉明组和联合组:肿瘤组织中H IF-1α和VEGF的灰度值均高于对照组,MVD的灰度值和PCNA增殖指数均低于对照组;H IF-1α和VEGF的灰度值以联合组最高,MVD和PCNA增殖指数以联合组最低,差异有统计学意义。阿霉素组:H IF-1α和VEGF的灰度值均高于对照组,但差异无统计学意义;低于联合组,差异有统计学意义;MVD低于对照组,但差异无统计学意义;高于联合组,差异有统计学意义;而PCNA增殖指数低于对照组,高于联合组,差异有统计学意义;各组间H IF-1α和VEGF的灰度值与MVD和PCNA增殖指数呈反向变化,直线相关分析显示均呈负相关。结论阿霉素可能协同苏拉明通过抑制H IF-1α和VEGF的表达,从而抑制肿瘤组织新生血管形成和肿瘤细胞增殖。Objective To study the regulation of Suramin in combination with Adriamyein and its effect on the HIF-1α and VEGF expressions in mice transplanted with lung adenocareinoma, Methods LA795 cells were subcutaneously inoeulated into the mammary fatty pad of T739 mice to establish the lung adenocareinoma model. After the treatment, 40 experimental mice were randomized into four groups （ten in each group）. Control group： every mouse was injected into abdominal cavity with 0. 2mt 0. 9% sodium chloride aqua everyday, 16 times total. Adriamycin groups： every mouse was injected into abdominal cavity with sodium chloride aqua （2 mg·kg^-1·d^-1 ） on the 4th, 11 th, and 18th days, Suramin groups： every mouse was injected with Suramin （ 10 mg·kg^-1·d^-1 ） once/day, 16 times total. Combination group： the dose is the combination of Adriamyeiu group and Suramin group, After transplantation, all mice were sacrificed on day ;24. The maximum length （a） and the width （b） of the subcutaneous tumors were measured, and the volume of the tumor＇s were calculated. The wet weights of the tumors were also recorded, The specimen of the tummors were fixed and , the HIF-1α and vascular endothelial growth factor （VEGF） expressions in tumor tissues, the subcutaneous tumor mierovessel density （MVD） and proliferating cell nuclear antigen （PCNA） were analyzed with immunohistochemistry and imaging system. Results The size and wet weight of the tumors in every treatment groups are significantly lower than those in the control group with the lowest in the combination group, The gray levels of HIF-1α and VEGF in tumor tissues of the suramin group and the combination group are higher than those of the control group. The MVD gray level and the PCNA proliferative index in the suramin group and the eombination group are lower than those in control group, The gray levels of HIF-1α and VEGF are the highest in the combination group, but the MVD gray level and the PCNA proliferative index are the lowest in the co

关 键 词：舒拉明/药理学 表柔比星/药理学 肺肿瘤 血管内皮生长因子类 缺氧 

分 类 号：R734.2[医药卫生—肿瘤]