托瑞米芬对大鼠Lewis肺癌雌激素受体表达及微血管生成影响的研究  

Effects of Toremifene on Estrogen Receptors Expression and Tumor Micro-angiogenesis in Rat Lewis Lung Carcinoma

作　　者：徐英[1] 颜浩[1] 韩娟[1] 章培[2] 徐淑晖[1] 周黎强[1] 

机构地区：[1]成都市第二人民医院呼吸内科,四川成都610017 [2]成都市第二人民医院病理科,四川成都610017

出　　处：《中国呼吸与危重监护杂志》2011年第6期581-585,共5页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：四川省卫生厅科研基金资助项目(编号:070373)

摘　　要：目的探讨托瑞米芬对大鼠Lewis肺癌雌激素受体(ER)及微血管生成的影响。方法采用Lewis肺癌细胞大鼠皮下移植瘤组织悬液,建立大鼠移植瘤模型。随机分为空白组、雌二醇组(0.006 mg/mL)、托瑞米芬低剂量组(0.25 mg/mL)和托瑞米芬高剂量组(5 mg/mL),每组10只。绘制肿瘤生长曲线,计算抑瘤率。采用免疫组化检测雌激素受体α(ERα)、雌激素受体β(ERβ)、血管内皮生长因子(VEGF)和血小板内皮细胞粘附分子1(PECAM-1)。应用图像分析软件分别计算ERα、ERβ及VEGF阳性表达的积分光密度,用Weinder方法对PECAM-1标记的微血管密度(MVD)计数。观察ER表达和VEGF表达及MVD计数的相关性。结果各组肿瘤随时间均呈现二次函数的增长趋势,托瑞米芬组的增长速度较空白组和雌二醇组慢(P<0.05)。雌二醇组抑瘤率为负值,托瑞米芬低剂量组抑瘤率为22.6%,托瑞米芬高剂量组抑瘤率为45.1%。雌二醇组ERα和VEGF表达及MVD计数均高于其他3组(P<0.05)。托瑞米芬剂量越高,ERα及VEGF表达及MVD计数越低(P<0.05)。ERα表达与VEGF表达、MVD计数呈正相关(P<0.05)。结论托瑞米芬具有一定的抑制肺癌生长的作用,推测可能与其抑制ERα介导的VEGF表达而发挥抑制肿瘤血管生成有关。Objective To explore the effect of toremifene on estrogen receptor（ER） expression and tumor micro-angiogenesis in rat Lewis lung carcinoma.Methods Cell suspension of rat Lewis lung carcinoma was implanted into 40 female Wistar rats subcutaneously.The rats were randomly divided into a control group,a estradiol group（0.006 mg/mL）,a low dose toremifene group（0.25 mg/mL） and a high dose toremifene group（5 mg/mL）.Tumor size was measured every 3 days and the tumor growth curve was charted.On 15th day,the tumor weight and the growth inhibition rate were measured.Immunohistochemical method was used to detect the expressions of estrogen receptor α（ERα）,estrogen receptor β（ERβ）,vascular endothelial growth factor（VEGF）,and platelet endothelial cell adhesion molecule-1（PECAM-1）.Integral optical density（IOD） of ERα,ERβ and VEGF was calculated by image analysis software.Quantitative method of Weidner with PECAM-1 was employed for microvessel density（MVD） count.Results Tumor size of the four groups all presented a quadratic function growth trend with time（P0.05）.Tumor growth speed was slower in the toremifene groups of low and high doses than those in the control group and the estradiol group.The growth inhibition rates of the estradiol group,the low dose toremifene group and the high dose toremifene group were-15.1%,22.6%,and 45.1%,respectively.The expressions of ERα,VEGF,and MVD in the estradiol group were significantly higher than those in the control group,the low dose toremifene group and the high dose toremifene group（all P0.05）.The expressions of ERα,VEGF,and MVD in the low dose toremifene group were significantly lower than those in the control group,but higher than those in the high dose toremifene group（all P0.05）.The expression of ERα was positively related to VEGF（r=0.664,P0.05） and MVD（r=0.593,P0.05）.Conclusion Toremifene can inhibit tumor growth,which maybe involved in inhibiting ERα mediated VEGF expression.

关 键 词：肺癌 托瑞米芬 雌激素受体亚型(ERα、ERβ) 血管内皮生长因子 微血管密度 

分 类 号：R734.2[医药卫生—肿瘤]