重组人血管内皮抑制素联合放射治疗对A549肺腺癌裸鼠移植瘤抗肿瘤效应研究  

Antitumor effect of radiation therapy associated with different patterns of human recombinant vascular endothelial in A549 lung adenocarcinoma nude mice transplantation tumor

作　　者：杨百霞 杨燕光 刘春 翟小刚 葛杨杨 曹飞 YANG Baixia;YANG Yanguang;LIU Chun;ZHAI Xiaogang;GE Yangyang;CAO Fei(Department of Radiotherapy,Affiliated Tumor Hospital of Nantong University/Nantong Tumor Hospital,Jiangsu 226361;Laboratory Animal Center of Nantong University)

机构地区：[1]南通大学附属肿瘤医院/南通市肿瘤医院放疗科,江苏226361 [2]南通大学实验动物中心

出　　处：《交通医学》2022年第1期5-9,共5页Medical Journal of Communications

基　　金：南通市卫生健康委员会科研立项课题(MB2020020)。

摘　　要：目的:探讨重组人血管内皮抑制素(恩度)与放疗不同联合对A549肺腺癌裸鼠移植瘤生长抑制作用的影响。方法:采用A549肺腺癌细胞裸鼠移植瘤模型,随机分为空白对照组(d 1~d 14注射0.9%氯化钠溶液),恩度组(d 1~d 14注射恩度)、恩度联合放射治疗组(联合组),联合组分为联合1组(d 1~d 14注射恩度+d 1、d 3放疗),联合2组(d 1~d 14注射恩度+d 5、d 7放疗)和联合3组(d 1~d 14注射恩度+d 9、d 11放疗),治疗14天。测量小鼠体重和移植瘤体积变化,计算抑瘤率。治疗结束后第10天处死裸鼠,作肿瘤组织病理学观察,免疫组化法检测肿瘤组织血管内皮生长因子(VEGF)表达及微血管密度(MVD)。结果:从治疗第7天起空白对照组肿瘤体积明显增大,生长曲线陡直,恩度组肿瘤体积增速次之,联合组肿瘤生长较缓慢,其中联合2组肿瘤体积增加最慢。裸鼠处死后测量显示,肿瘤质量和体积恩度组小于空白对照组,联合各亚组小于空白对照组和恩度组,差异均有统计学意义(P<0.05),其中联合2组抑瘤率最高,达到77.8%。病理检查显示,恩度组部分肿瘤细胞出现粘液变性,联合亚组肿瘤细胞坏死、变性显著。与空白对照组比较,恩度组、联合1组、联合2组、联合3组VEGF表达降低,MVD减小,差异均有统计学意义(P<0.05),联合1、联合2、联合3各亚组间比较,VEGF表达及MVD的差异均无统计学意义(P>0.05)。结论:重组人血管内皮抑制素联合放射治疗对A549肺腺癌细胞裸鼠移植瘤的抗肿瘤效果明显优于单用重组人血管内皮抑制素,可能与恩度能有效减少肿瘤组织血供,增敏放疗作用有关。Objective:To explore growth inhibition effects of radiotherapy combined different modes of recombinant human endostatin in A549 lung adenocarcinoma nude mice transplantation.Methods:Nude mice transplantation tumor model(A549 lung adenocarcinoma cells)were randomly divided into blank control group,recombinant human endostatin group and radiation therapy associated with human recombinant vascular endothelial group.Weight change and tumor diameter in mice was measured and recorded.Mice were sacrificed 10 days after irradiation,then tumor tissue morphological changes were observed by HE staining method and the expressions of VEGF and MVD in tumor tissues were detected by immunohistochemical method.Results:From the 7th day of treatment,the tumor volume in the control group increased significantly,followed by endostar group,and the tumor volume in the combined group increased the least.The tumor mass and volume of endostar group were smaller than that of the control group,and the combined subgroups were smaller than that of the control group(P<0.05).The combined 2 group had the highest tumor inhibition rate,up to 77.8%.Some tumor cells in endostar group showed mucinous degeneration,while tumor cells in combined group showed significant necrosis and degeneration in pathological examination.Compared with the control group,VEGF expression and MVD significantly decreased in the endostar,combined 1,combined 2 and combined 3 groups(P<0.05).There was no significant difference in VEGF expression and MVD between the combined group 1,combined group 2 and combined group 3(P>0.05).Conclusion:Antitumor effect of radiation therapy with human recombinant vascular endothelial inhibition group was better than in the other groups.Antitumor effect was related with irradiation time and it was most significant when radiotherapy was 6 days after administration.

关 键 词：重组人血管内皮抑制素 放射治疗 A549肺腺癌细胞 裸鼠移植瘤 抑瘤率 血管内皮生长因子 微血管密度 

分 类 号：R734.2[医药卫生—肿瘤]