人源抗c-Met单链抗体腹腔注射可抑制A549肺腺癌荷瘤小鼠移植瘤生长  

Intraperitoneal injection of human-derived anti-c-Met single-chain antibody inhibits the growth of transplanted tumours in A549 lung adenocarcinoma-loaded mice

作　　者：安然 刘明珠 张露 彭上 甄翔程 闵静婷 李正红 AN Ran;LIU Mingzhu;ZHANG Lu;PENG Shang;ZHENG Xiangcheng;MIN Jingting;LI Zhenghong(Department of Physiology,School of Public Foundation,School of Basic Medical Sciences,Bengbu Medical University,Bengbu 233030,China;Department of Physiology,School of Life Sciences,School of Basic Medical Sciences,Bengbu Medical University,Bengbu 233030,China;Department of Physiology,School of Basic Medical Sciences,Bengbu Medical University,Bengbu 233030,China)

机构地区：[1]蚌埠医科大学公共基础学院生理学教研室,安徽蚌埠233030 [2]蚌埠医科大学生命科学院生理学教研室,安徽蚌埠233030 [3]蚌埠医科大学基础医学院生理学教研室,安徽蚌埠233030

出　　处：《细胞与分子免疫学杂志》2024年第6期549-555,共7页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81472656);安徽省重点研究与开发计划(201904a07020019);安徽省高校自然科学研究重大项目(2022AH040224);国家级高校创新训练项目(202310367011);蚌埠医学院研究生创新项目(Byyc23015)。

摘　　要：目的 该实验旨在验证间质上皮转化单链抗体(Met scFv)在体内对皮下移植瘤裸鼠的抗肿瘤作用。方法 建立裸鼠肿瘤模型,皮下注射A549肺腺癌细胞,成瘤后通过腹腔注射IRDye680 LT N-羟基琥珀酰亚胺(NHS)酯标记的Met scFv,借助小动物成像仪进行实时监测以观察该抗体在荷瘤小鼠体内的动态分布情况,检测肿瘤组织细胞c-Met与抗体的亲和力,定期尾静脉注射Met scFv,观察肿瘤体积变化并绘制肿瘤生长曲线。免疫组织化学染色法检测Met scFv是否能有效结合肿瘤组织中的c-Met抗原。结果 裸鼠体内分布结果表明,在最初的3 h内,Met scFv主要分布于腹腔内。经过大约48 h,荧光信号开始在肿瘤组织中聚集。瘤体免疫组织化学染色结果显示,肿瘤组织中c-Met高表达;定期尾静脉注射Met scFv,可使小鼠瘤体生长明显减缓。结论 Met scFv在体内特异性识别肿瘤细胞且表现出显著的抗肿瘤活性。Objective To verify the anti-tumor effect of the mesenchymal-epithelial transition single-chain antibody(Met scFv)on subcutaneously transplanted tumors in nude mice.Methods A tumor model was established in nude mice by subcutaneous injection of A549 lung adenocarcinoma cells.Once the tumors were formed,IRDye680 LT N-hydroxysuccinimide(NHS)ester-labeled Met scFv was administered intraperitoneally.Real-time monitoring was conducted using a small animal imager to observe the dynamic distribution of the antibody in tumor-bearing mice.The affinity between c-Met and the antibody in tumor cells was detected.Tumor volume changes were observed and the tumor growth curve were plotted following regular tail vein injections of Met scFv.Immunohistochemical staining was employed to determine whether Met scFv could effectively bind to the c-Met antigen in tumor tissues.Results The distribution of Met scFv in nude mice showed that it was primarily located in the peritoneal cavity within the first 3 hours.After approximately 48 hours,fluorescent signals began to accumulate in the tumor tissue.Immunohistochemical staining of the tumors revealed high expression of c-Met in the tumor tissues;regular tail vein injections of Met scFv significantly slowed down the growth of tumors in mice.Conclusion Met scFv specifically recognizes tumor cells in vivo and exhibites significant anti-tumor activity.

关 键 词：细胞间质上皮转化(c-Met) 单链抗体(scFv) 抗原识别 抗肿瘤活性 

分 类 号：R392-33[医药卫生—免疫学] S852.43[医药卫生—基础医学] R392.12[农业科学—基础兽医学] R734.2[农业科学—兽医学]