ABCG2特异性肺腺癌单链抗体的裸鼠体内放免显像及其抑瘤作用  

Radioimmunoimaging and anti-tumor effect of anti-ABCG2 single-chain antibody in nude mice with lung adenocarcinoma transplantation

作　　者：赵文思[1] 周寒静 罗弋[1] 

机构地区：[1]重庆医科大学附属第一医院肿瘤科,重庆400016

出　　处：《第三军医大学学报》2016年第24期2600-2605,共6页Journal of Third Military Medical University

基　　金：国家自然科学基金青年科学基金(81302018);肿瘤科国家临床重点专科建设项目[国卫办医函(2013)544号]~~

摘　　要：目的观察ABCG2特异性肺腺癌单链抗体(scFv)在裸鼠体内的放免显像和代谢动力学特征,并探讨其对肿瘤生长的作用。方法采用不同浓度梯度scFv处理肺腺癌细胞后,Western blot检测ABCG2靶蛋白表达量的变化;CCK-8检测细胞增殖能力改变并绘制生长曲线;流式细胞术检测细胞凋亡和周期变化;放射性核素131I标记抗体后行裸鼠体内生物分布和SPECT/CT放免显像研究;进一步建立移植瘤模型检测scFv的体内抑瘤能力。结果 scFv干预肺腺癌细胞后导致ABCG2蛋白表达水平较对照组显著降低,并明显抑制细胞增殖,诱导细胞凋亡和细胞周期阻滞(P<0.05)。裸鼠体内生物分布和放免显像结果显示该scFv具有良好的代谢动力学特征,表现为高效、快速的肿瘤靶部位特异性结合及体内清除能力。结论肺腺癌ABCG2 scFv具有良好的放免显像效果,并显示出较好的代谢动力学、亲肿瘤和抗肿瘤特性,对肿瘤的生长有抑制作用。Objective To characterize the radioimmunoimaging and metabolic dynamics of anti-ATP- binding cassette subfamily G member 2 （ABCG2） single-chain antibody of lung adenocarcinoma in nude mice and its anti-tumor capacity. Methods Human lung adenocarcinoma A549 cells were treated with different concentrations of anti-ABCG2 antibody, a self-constructed single-chain variable Western blotting was performed to evaluate the expression of ABCG2 protein. detected by CCK-8 assay. Cell apoptosis and changes fragment （ seFv ） antibody. Cell proliferation rate was of cell cycle were analyzed by flow cytometry. Xenograft models were generated to determine the anti-tumor capacity of this antibody. 131 I-labelled scFv antibody was then prepared and used for the biodistribution study and SPECT/CT imaging in tumor-bearing mice. Results The scFv antibody resulted in antibody-mediated down-regulation of ABCG2 protein, proliferation inhibition, apoptosis, and cell cycle arrest in lung adenocarcinoma cells. The biodistribution and radioimmunoimaging analyses showed favorable effects of scFv antibody in fast penetration, specific binding to target tissue and rapid blood clearance, indicating its superior pharmacokinetic properties. Conclusion The specific single-chain antibody against ABCG2 of lung adenocarcinoma exhibits satisfactory radioimmunoimaging effect, better pharrnacokinetics, tumoraffin and anti-tumor activity. This may provide a strong basis for subsequent body visualization of lung adenocarcinoma and to explore its potential as a delivery vehicle in immunotherapy.

关 键 词：肺腺癌 单链抗体 ABCG2 代谢动力学 肿瘤抑制 

分 类 号：R730.44[医药卫生—肿瘤]