土贝母苷甲在非小细胞肺癌异种移植鼠模型中抑制肿瘤血管生成的研究  

A Study on Tubeimoside-1 in Inhibition of Tumor Angiogenesis in Non-small-cell lung Cancer Xenograft Rat Models

作　　者：李铁英[1] 李华[1] 战涛[1] 张放[2] 

机构地区：[1]本溪市本钢总医院呼吸科,辽宁本溪117000 [2]中国医科大学附属第一医院呼吸疾病研究所,沈阳110001

出　　处：《解放军医药杂志》2016年第11期56-60,共5页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：辽宁省科技计划项目(2010225034)

摘　　要：目的研究土贝母苷甲对肿瘤血管生成的影响及相应的分子机制。方法将20只CD-1裸鼠随机分为对照组(生理盐水)和土贝母苷甲组(TBMS-I),每组各10只;皮下注射接种非小细胞肺癌(NSCLC)浓度为1×107/ml的NCI-H460单细胞悬液100μl,接种1 d后开始腹腔给药,TBMS-I给药浓度为5 mg/kg,1/d,绘制肿瘤生长曲线,并对瘤体积和瘤重进行统计学分析;观察瘤内微血管密度;采用WST-1检测TBMS-I对内皮细胞、肿瘤细胞的抑制作用;Western blot检测TBMS-I对裸鼠内皮细胞e END2的VEGFR-2(KDR)和Tie2的表达的影响。结果 TBMS-I可显著抑制NSCLC的形成,减少瘤内血管密度,诱导内皮细胞凋亡且不减弱肿瘤细胞的活性,降低裸鼠内皮细胞e END2膜上VEGFR-2(KDR)和Tie2的表达,与对照组比较差异均有统计学意义(P<0.05)。结论 TBMS-I能够抑制肿瘤血管的生成,其作用机制可能与下调VEGF/VEGFR2和Ang2/Tie2信号传导途径相关。Objective To investigate effect of Tubeimoside-1（TBMS-1） on tumor angiogenesis in non-smallcell lung cancer（NSCLC） xenograft rat models and its molecular mechanism.Methods A total of 20 CD-1 nude mice were randomly divided into control group（n = 10） and TBMS-1 group（n = 10）.All nude mice received 100μL NClH460 single cell suspension with 1 × 107/ ml NSCLC by subcutaneous injection.TBMS-1 group received intraperitoneal administration 1 d after vaccination with 5 mg / kg TBMS-1 concentration,and tumor growth curve was drawn,and statistical analysis was performed for volume and weight of the tumor.The microvessel density in tumor was observed,and inhibitory effects of TBMS-1 on endothelial and tumor cells were detected by WST-1 assay.Effects of TBMS-1 on VEGFR-2（KDR） and Tie2 expressions in e END2 endothelial cells were detected by Western blot.Results TBMS-1（5mg/kg）significantly inhibited growth,and reduced microvessel density in tumor.In vitro,TBMS-1 induced endothelial cell apoptosis without decreasing viability of tumor cells,and it decreased VEGFR-2（KDR） and Tie2 expressions in e END2 endothelial cells,and the differences were statistically significant compared with those in control group（P〈0.05）.Conclusion TBMS-1 can inhibit tumor angiogenesis,and its mechanism of action may be related to down-regulation of VEGF / VEGFR2 and Ang2 / Tie2 signaling path.

关 键 词：癌 非小细胞肺 土贝母苷甲 血管生成 血管内皮生长因子 裸鼠 

分 类 号：R730.26[医药卫生—肿瘤]