选择性COX-2抑制剂联合顺铂对肺癌新生血管的影响及机制研究  

Cox-2 inhibitors in combination with cisplatin for lung cancer research progress of angiogenesis

作　　者：魏慧 张卿[2] Wei Hui;Zhang Qing(Department of Respiratory and Critical Care Medicine,People′s Hospital of Inner Mongolia,Hohhot 010010,China;Department of Respiratory Medicine,the First Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010010,China)

机构地区：[1]内蒙古自治区人民医院呼吸与危重症医学科,呼和浩特010010 [2]内蒙古医科大学第一附属医院呼吸内科,呼和浩特010010

出　　处：《国际呼吸杂志》2020年第7期487-492,共6页International Journal of Respiration

摘　　要：目的研究选择性环氧化酶2(COX-2)抑制剂尼美舒利(NIM)单独应用以及联合顺铂(DDP)对肺癌A549细胞裸鼠移植瘤血管生成的影响及其机制,为肺癌的治疗提供新思路。方法培养肺癌A549细胞,构建肺癌A549裸鼠移植瘤模型。依据随机数字表法将研究对象分为4组进行药物干预:对照组、NIM组、DDP组、NIM+DDP组,每组8只,观察一般状态。给药后第22天处死裸鼠,获取肿瘤组织,测量称取瘤重、瘤径,计算并比较各组体积抑瘤率。用CD31标记微血管,采用微血管计数法检测各组微血管密度。采用免疫组织化学检测肺癌A549裸鼠移植瘤内血管内皮生长因子的表达。结果本研究成功构建肺癌A549裸鼠移植瘤模型。NIM+DDP组第9、13、17、21天的移植瘤体积增长较其他3组慢(P值均<0.001)。NIM+DDP组体积抑瘤率最大。NIM+DDP组较其他3组移植瘤微血管密度低(F=27.861,P<0.001)。结论选择性COX-2抑制剂单独使用有抑制新生血管生成的作用,推测选择性COX-2抑制剂具有抗肿瘤能力,可能成为肺癌靶向治疗因子。选择性COX-2抑制剂联合DDP对新生血管因子表达的抑制效果更显著,对肺癌A549细胞裸鼠移植瘤的生长的抑制更显著。Objective To investigate the selective cyclooxygenase-2(COX-2)inhibitor nimesulide(NIM)and in combination with cisplatin(DDP)on A549 cells in nude mice transplanted tumor angiogenesis and its mechanism for the treatment oflung cancer in vivo.Methods Lung cancer A549 cells and established A549 lung xenografts in nude mice model.According to the method of random number table,the subjects were divided into four groups for drug intervention:control group,NIM group,DDP group,NIM+DDP group,each group of 8,and the general state was observed.Mice were killed by cervical dislocation on 22nd days,then obtained tumor tissues,weighed tumor,measured tumor diameter and calculated tumor inhibition rate.To clarify the influence of nimesulide alone or in combination with cisplatin in A549 lung cancer xenograft tumor neovascularization,labeled microvessel with CD31 and counted microvessel density using microvessel counts.Immunohistochemistry was used to detect the expression of endovascular endothelial growth factor in lung cancer A549 in nude mice.Results In this study,a nude mouse model of lung cancer A549 was successfully constructed.The tumor volume of NIM+DDP group increased more slowly than the other three groups on the 9th,13th,17th and 21st day(all P<0.001).Nim+DDP group had the largest tumor inhibition rate.The microvessel density of NIM+DDP group was lower than that of the other three groups(F=27.861,P<0.001).Conclusions The selective COX-2 inhibitors could inhibit angiogenesis,suggesting that selective COX-2 inhibitors have anti-tumor capabilities and may be used as a lung cancer targeted therapy.The selective COX-2 inhibitor combined with cisplatin had a more significant inhibitory effect on the expression of neovascularization factors and the growth of transplanted tumor in nude mice with lung cancer A549 cells.

关 键 词：肺肿瘤 血管内皮生长因子类 环氧化酶2抑制剂 

分 类 号：R734[医药卫生—肿瘤]