参麦注射液联合多西他赛对荷瘤裸鼠肿瘤血管生长的抑制作用及其机制  

The antiangiogenetic effect and mechanism of ShenMai injection combined with docetaxel on transplanted human carcinoma in nude mice

作　　者：钱晓萍[1] 马亚军[1] 胡静[1] 胡文静[1] 禹立霞[1] 刘宝瑞[1] 

机构地区：[1]南京大学医学院附属鼓楼医院肿瘤中心,江苏南京210008

出　　处：《中国癌症杂志》2009年第4期252-256,共5页China Oncology

基　　金：江苏省自然基金(BK2006005)

摘　　要：背景与目的:血管生成在肿瘤从良性向恶性转变、癌细胞进入血液循环、转移灶的发展中都起着重要作用。本研究探讨参麦注射液10联合多西他赛对裸鼠人大肠癌LOVO皮下移植瘤血管生成抑制作用及其机制。方法:通过建立裸鼠人大肠癌LOVO细胞皮下移植瘤模型,将荷lovo肿瘤裸鼠随机分为4组,(每组5只):①空白对照生理盐水组,生理盐水0.4ml,每天腹腔注射。②参麦组(20ml/kg),每天给药,连续给药2周,腹腔注射。③泰素帝组(5mg/kg),每3天给药1次,连续2周,腹腔注射。④参麦+泰素帝组,参麦(20ml/kg)连续给药2周,腹腔注射;泰素帝(5mg/kg),每3天给药1次,连续2周,腹腔注射。观察参麦注射液,联合多西他赛的抑瘤作用,并采用免疫组化法检测参麦注射液联合多西他赛对肿瘤组织微血管密度、VEGF、TSP1蛋白表达的影响。结果:参麦注射液的抑瘤率为49%,多西他赛的抑瘤率为72.4%,两者联合的抑瘤率为80.0%。参麦注射液、多西他赛及联合用药均能降低肿瘤微血管密度(P分别为0.007,0.003,0.001),下调VEGF蛋白的表达(P分别为0.011,0.002,<0.001)。参麦注射液对TSP1蛋白无调节作用,多西他赛及联合用药可上调TSP1蛋白的表达。结论:①参麦注射液与多西他赛可能通过抑制肿瘤血管生成而发挥抗肿瘤作用,两者联合应用具有次加效应;②下调VEGF蛋白可能是参麦注射液与多西他赛抗血管生成作用机制之一;③上调TSP1蛋白可能是多西他赛抗血管生成另一作用机制,而参麦注射液对此无调节作用。Background and purpose： Angiogenesis plays an important role in the process of tumorigenesis, entrance of cancer ceils into the blood circulation, and the development of metastatic loci. This study investigated the antiangiogenetic effect and mechanism of ShenMai Injection combined with Docetaxel on transplanted human carcinoma of colon LOVO cells in nude mice. Methods： The tumor model was established by injecting human carcinoma of colon LOVO ceils under the nude mice armpit skin of its right forearm. Nude mice with lovo cancer cells are randomized divided into 4 groups （5 in each group）：①Control group： NS 0.4 ml intraperitoneal injection daily; ②ShenMai group： 20 ml/kg, intraperitoneal injection daily for 2 weeks; ③Docetaxel group： 5 mg/kg, intraperitoneal injection every three days for 2 weeks; ④ShenMai＋docetaxel group： ShenMai 20 ml/kg and docetaxel 5 mg/kg intraperitoneal injection every three days for 2 weeks.We observed the tumor-inhibitory rates of ShenMai Injection combined with docetaxel and also studied the expression of MVD,VEGF and TSP1 in tumor tissue by means of immunohistochemistry. Results： Tumor-inhibitory rates of ShenMai group and docetaxel group were 49.0% and 72.4%, respectively. The tumor-inhibitory rate of ShenMai combined with docetaxel group was 80.0%. They all could significantly suppress the level of MVD（P=0.007,0.003,0.001, respectively）,VEGF（P=0.011,0.002,〈0.00 1, respectively）. Docetaxel,the combined use of ShenMai and Docetaxel could significantly raise the level of TSP1 protein,while ShenMai was negative. Conclusion： ①ShenMai and Docetaxel could inhibit the angiogenesis of tumor. ②Both ShenMai and Docetaxel could reduce the expression of VEGF protein.③Docetaxel could raise the expression of TSP 1 protein while ShenMai could not.

关 键 词：血管生成 肿瘤 微血管密度 血管内皮生长因子 凝血栓敏感蛋白-1 

分 类 号：R73-361[医药卫生—肿瘤]