内皮抑素联合化学疗法治疗肿瘤进展后二线使用协同抗肿瘤作用研究  

he Synergistic Anti-tumor Efect of Endostatin on a Tumor-progression Murine Lung Cancer Model

作　　者：张炜[1] 伍璐[1] 王资[1] 刘燕杨[1] 罗锋[1] 

机构地区：[1]四川大学华西医院肿瘤中心,成都610041

出　　处：《华西医学》2013年第7期989-993,共5页West China Medical Journal

基　　金：国家自然科学基金(30972971);四川省科技厅科技支撑计划资助项目(2010FZ0089)~~

摘　　要：目的建立重组人内皮抑素(恩度)联合顺铂一线治疗肿瘤进展的小鼠模型,继续应用内皮抑素联合紫杉醇二线治疗,研究内皮抑素协同紫杉醇抗肿瘤的作用及其机制。方法建立小鼠Lewis肺癌移植瘤动物模型,内皮抑素联合顺铂治疗后观察肿瘤生长情况,遴选出肿瘤进展小鼠16只,随机留取1只,余15只小鼠随机分成紫杉醇组和联合用药组治疗,观察疗效。另取上述肿瘤进展小鼠1只,剥离肿瘤组织,重新接种,将成瘤小鼠随机分成生理盐水组,紫杉醇组及联合用药组治疗,观察疗效。治疗结束后24 h处死所有小鼠,采用免疫组织化学CD31单克隆抗体标记检测微血管密度(MVD),采用原位末端转移酶(TUNEL)检测细胞凋亡。结果 15只肿瘤进展小鼠中,联合用药组相比紫杉醇组生存时间无明显延长,但肿瘤体积增长较慢;而在重新接种成瘤的小鼠中,联合用药组较其余各组微血管密度明显减低(P<0.05),凋亡指数明显增加(P<0.05),肿瘤体积抑制明显。结论在内皮抑素联合顺铂治疗肿瘤进展的小鼠模型中,继续应用内皮抑素治疗与紫杉醇有较明显的协同抗肿瘤作用。Objective To investigate the synergistic anti-tumor effect and mechanism of endostatin combined with paclitaxel on a tumor-progression murine lung cancer model.Methods The Lewis lung cancer xenograft C57BL/6 mice were treated with endostatin and cisplatin.One mouse was randomly selected out from all the tumor-progression animals,and then the others were randomly divided into paclitaxel group and combined group.Tumor growth and mice survival time were observed.The selected tumor-progression mouse was killed and the tumor tissue was milled through a 200 mesh cell sieve.The xenograft C57BL/6 mice which were implanted with these cells were randomly divided into saline group,paclitaxel group and combined group,and tumor growth was observed.In twenty-four hours after the last treatment,all the mice were killed.Microvessel density（MVD） was marked by CD31 antibody and cell apoptosis was examined by TUNEL staining.Results In 15 tumorprogression mice,tumor grew more slowly in the combined group than in the paclitaxel group,but no difference of survival time was found between these two groups.In mice implanted tumor again,MVD was significantly lower in combined group than in other groups（P0.05）,but apoptosis index was higher（P0.05）.Conclusion In a tumor-progression murine lung cancer model treated with endostatin and cisplantin,synergistic anti-tumor effect of endostatin combined with paclitaxel is found.

关 键 词：内皮抑素 肿瘤进展 化学疗法 协同作用 

分 类 号：R73-36[医药卫生—肿瘤]