利用结直肠癌类器官模型评估化疗药物药效  

Evaluation of chemotherapy drug efficacy using organoids model of colorectal cancer

作　　者：果月红 周凡琦 吴熙 张冠南[3] 王芳[1] 余佳[1] GUO Yuehong;ZHOU Fanqi;WU Xi;ZHANG Guannan;WANG Fang;YU Jia(Department of Biochemistry and Molecular Biology,Institute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC,Beijing 100005;Department of Comprehensive Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021;Department of General Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China)

机构地区：[1]中国医学科学院基础医学研究所,北京协和医学院基础学院,生物化学与分子生物学系,北京100005 [2]中国医学科学院,北京协和医学院肿瘤医院/国家肿瘤中心/国家肿瘤临床研究中心综合肿瘤科,北京100021 [3]中国医学科学院,北京协和医学院,北京协和医院基本外科,北京100730

出　　处：《基础医学与临床》2025年第4期456-464,共9页Basic and Clinical Medicine

基　　金：国家自然科学基金(82470123)。

摘　　要：目的构建人结直肠癌类器官并进行化疗药物药效评估。方法利用体外分离的人结直肠癌组织,采用3D类器官培养方法建立生物样结肠癌3D培养物;并使用免疫组化方法对肿瘤类器官和原发肿瘤组织进行结直肠癌分子标记物染色;使用肿瘤类器官进行药物敏感性试验,分别给予不同浓度化疗药物5-氟尿嘧啶、奥沙利铂、伊立替康;采用3D细胞活力检测法测定药物处理前后的类器官活性。结果成功建立了5例患者样本来源的结直肠癌类器官;免疫组化结果显示CK20、Ki67和Villin蛋白的表达在肿瘤类器官与原发肿瘤中相似,且肿瘤类器官保留了与原发肿瘤相似的组织学特征;不同患者来源的肿瘤类器官表现出对不同化疗药物差异的敏感性。结论人结直肠癌类器官模型可以反应对不同化疗药物的不同敏感性,可为指导临床制订患者的个性化治疗提供参考。Objective To establish human colorectal cancer(CRC)organoids and to evaluate the efficacy of chemotherapy drugs.Methods Patient-derived CRC cells were cultured to form organoids.The CRC organoids and original tissues were stained with molecular markers of CRC immunohishtochemically.CRC organoids were used to test drug sensitivity and different concentrations of chemotherapy drugs 5-fluorouracil,oxaliplatin and irinotecan were given respectively;Organoid activity before and after drug treatment was measured by 3D cell viability assay.Results The patient-derived organoids(PDO)from 5 CRC tissues were successfully established.The expression of CK20,Ki67 and Villin proteins was similar in organoids and in original tumor.The organoids retained histologcial features similar to those of the original tumors.Different PDO showed differential sensitivity to different chemotherapy drugs.Conclusions CRC-PDO can dispaly their different sensitivities to different chemotherapy drugs,and could provide valuble reference for personalized treatment for CRC patients.

关 键 词：结直肠癌类器官 药物敏感性 

分 类 号：R733.7[医药卫生—肿瘤]