患者源性非小细胞肺癌异种移植模型的建立及个体化治疗策略研究  

Establishment of patient derived xenograft model with non-small cell lung cancer and study on individualized treatment strategy

作　　者：刘建辉 李惠 谭邓旭 秦靖 张彩勤 师长宏 LIU Jianhui;LI Hui;TAN Dengxu;QIN Jing;ZHANG Caiqin;SHI Changhong(Baoguang Branch of Baoji Hospital Affiliated to Xi'an Medical College,Baoji 721006,China;Experimental Animal Center of Air Force Military Medical University,Xi'an 710032,China)

机构地区：[1]西安医学院附属宝鸡医院宝光分院,陕西宝鸡721006 [2]空军军医大学实验动物中心,陕西西安710032

出　　处：《延安大学学报（医学科学版）》2023年第3期37-43,共7页Journal of Yan'an University:Medical Science Edition

摘　　要：目的通过将患者非小细胞肺癌(non-small cell lung cancer,NSCLC)临床手术标本接种于BALB/c裸小鼠,建立相应的移植瘤模型,为肺癌患者个体化治疗药物的筛查和临床前疗效的评估提供理想的动物模型。方法收集患者非小细胞肺癌手术标本并将其植入裸鼠体内建立患者源性异种移植(patient-derived xenograft,PDX)模型,分析病理组织学形态,检测人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)和表皮生长因子受体(epidermal growth factor receptor,EGFR)的表达,以及潜在靶标单胺氧化酶A(monoamineoxidase A,MAOA)的表达。进一步在此患者源性NSCLC异种移植模型中评估靶向药、临床一线化疗药物顺铂的抗肿瘤功效。结果成功建立了患者源性的NSCLC异种移植瘤模型,该模型保留了源肿瘤组织病理学形态,且EGFR、MAOA呈阳性表达。使用EGFR抑制剂奥希替尼联合顺铂体现出良好的治疗效果;此外,MAOA抑制剂氯吉林也具有良好的抗肿瘤潜能,与顺铂联合治疗效果更加显著。结论建立了NSCLC异种移植模型,保留了原发肺癌的分子特征,可以作为探索肿瘤个体化治疗方案的有效工具。Objective By inoculating non-small cell lung cancer(NSCLC)clinical surgical specimens into BALB/c nude mice to establish corresponding patient derived xenograft(PDX)models,to obtain a reliable animal model for the screening of individualized treatment drugs and the evaluation of preclinical efficacy in the patients with lung cancer.Methods Fresh surgical specimens of NSCLC were collected and implanted into nude mice to establish PDX model.Histological morphology was analyzed,human epidermal growth factor receptor 2(HER2)and epidermal growth factor receptor(EGFR)gene expression were detected,and the expression of the potential target monoamine oxidase A(MAOA)was performed.Furthermore,the anti-tumor efficacy of targeted drugs and clinical first-line chemotherapy drug cisplatin was evaluated in this PDX model.Results A patient derived NSCLC xenograft model was successfully established.This model preserves the histopathological morphology of the original tumor and EGFR activated mutations,and MAOA is positively expressed.The combination of EGFR inhibitor osimertinib with cisplatin showed apparent therapeutic effect;In addition,the MAOA inhibitor clorgyline also displays better anti-tumor potential,and the combined effect with cisplatin is more significant.Conclusion A NSCLC xenograft model that preserves the molecular characteristics of primary lung cancer had established and the model can serve as an effective tool for exploring individualized treatment strategy for tumors.

关 键 词：非小细胞肺癌 患者源性异种移植模型 表皮生长因子受体 单胺氧化酶A 

分 类 号：R734.2[医药卫生—肿瘤]