塞来昔布联合厄罗替尼对人肺癌裸鼠移植瘤生长及血管生成的影响  

Effects of erlotinib combined with celecoxib on growth and angiogenesis of human lung cancer xenograft model

作　　者：董雪丽[1] 牟晓燕[1] 刘庆亮[1] 孙杰[1] 

机构地区：[1]山东大学附属省立医院东院保健综合一科,济南250000

出　　处：《山东大学学报（医学版）》2013年第2期49-52,共4页Journal of Shandong University:Health Sciences

基　　金：山东省科技发展计划(2010GSF10253);山东省自然科学基金(ZR2009CM125)

摘　　要：目的探讨厄洛替尼和塞来昔布联合阻断表皮生长因子受体(EGFR)和环氧合酶-2(COX-2),对人肺腺癌裸鼠移植瘤生长及血管形成的影响。方法人肺癌细胞A549接种于裸鼠皮下,成瘤后随机分为4组:对照组、厄洛替尼组、塞来昔布组、塞来昔布和厄洛替尼联合用药组,给予灌胃处理,观察裸鼠生长状况,每周两次测量肿瘤大小,绘制肿瘤生长曲线。40 d后处死裸鼠,称取移植瘤质量。采用免疫组化检测肿瘤微血管密度(MVD),ELISA法检测裸鼠血清中血管内皮生长因子(sVEGF)的含量,Western Blot法检测Bcl-2、Bax蛋白的表达情况并计算Bcl-2/Bax的值。结果联合用药组肿瘤明显小于塞来昔布组、厄洛替尼组和对照组(P<0.05)。联合用药组微血管数目、sVEGF的含量明显小于塞来昔布组、厄洛替尼组和对照组(P<0.05)。厄洛替尼组Bcl-2的表达明显小于对照组(P<0.05),塞来昔布组Bcl-2的表达与对照组相比差异无统计学意义(P>0.05),联合用药组Bcl-2的表达与对照组、塞来昔布组、厄洛替尼组相比均明显降低(P<0.05)。Bax的表达在各组之间差异无统计学意义(P>0.05)。联合用药组Bcl-2/Bax较塞来昔布组、厄洛替尼组明显降低(P<0.05)。结论塞来昔布联合厄洛替尼相对厄洛替尼或塞来昔布明显抑制人肺癌移植瘤的生长。其中减少微血管生成、增加肿瘤细胞的凋亡可能为其抗肿瘤机制。Objective To explore the effects of erlotinib combined with celecoxib on the tumor growth and angiogenesis of lung cancer xenografts in nude mice. Methods Human lung cancer cell A.549 was subcutaneously injected to establish the nude mice xenograft model. The nude mice with tumor were randomly divided into four groups：the control group, the celecoxib group, the eflotinib group and the combined group. All the mice were given the gavage administration. The status of the mice were observed everyday , and the volume of the tumor was measured twice a week to obtain the tumor growth curve. The mice were put to death to collect the tumor tissues after 40 days. The microvessel density （MVD） was detected by the immunohistochemistry analyses and the expressions of Bcl-2 and Bax were detected by Western Blotting. Blood samples were collected to detect the sVEGF level by ELISA. Results The tumor volumes of the combined group were significantly smaller compared with the control group, the celecoxib group and the erlotinib group（P 〈 0.05）The microvessel density and the sVEGF level of the combined group were decreased compared with the control group, the celecoxib group and the erlotinib group（ P 〈 0.05 ）. The Bcl level of the eflotinib group waslower compared with the control group. There was no significant difference of the Bcl-2 level between the celecoxib group and the control group （ P 〉 0.05 ）. The Bcl-2 level of the combined group is lower compared with the control group, the celecoxib group and the erlotinib group（ P 〈 0.05 ）. There was no significant difference of the Bax level among the control group, the celecoxib group and the combined group（ P 〉 0.05 ）. The value of Bcl-2/Bax of the combined group was lower compared with the celecoxib group and the erlotinib group （ P 〈 0.05 ）. Conclusion Erlotinib combined with celecoxib have more effective growth inhibition on the human lung cancer xenograft model than eflotinib or celecoxib separately. The possible mechanism may be relat

关 键 词：肺腺癌 塞来昔布 厄洛替尼 裸鼠移植瘤 微血管生成 

分 类 号：R734.2[医药卫生—肿瘤]