胃癌类器官模型应用于个性化药物筛查的可行性  

Feasibility of gastric cancer organoid models for personalized drug screening

作　　者：范洪凯 管瑛瑛 王路敏 曾凡伟 尹毅锐 Fan Hongkai;Guan Yingying;Wang Lumin;Zeng Fanwei;Yin Yirui(Department of General Surgery,Zhongshan Hospital(Xiamen Hospital),Fudan University,Xiamen 361015,Fujian Province,China;Department of Pathology,Zhongshan Hospital(Xiamen Hospital),Fudan University,Xiamen 361015,Fujian Province,China;Department of Pharmacy,Zhongshan Hospital(Xiamen Hospital),Fudan University,Xiamen 361015,Fujian Province,China;Xiamen BCSS Biotechnology Co.,Ltd.,Xiamen 361100,Fujian Province,China)

机构地区：[1]复旦大学附属中山医院厦门医院普通外科,福建省厦门市361015 [2]复旦大学附属中山医院厦门医院病理科,福建省厦门市361015 [3]复旦大学附属中山医院厦门医院药剂科,福建省厦门市361015 [4]厦门博创盛世生物技术有限公司,福建省厦门市361100

出　　处：《中国组织工程研究》2025年第25期5345-5350,共6页Chinese Journal of Tissue Engineering Research

基　　金：厦门市医疗卫生指导性项目(3502Z20209055),项目负责人:范洪凯;福建省卫健委科技计划项目(2020QNB063),项目负责人:尹毅锐。

摘　　要：背景:术后辅助化疗是治疗胃癌的常用方法,但患者对化疗的反应存在很大的差异,需要一种新的临床治疗前模型,来指导胃癌患者的个性化药物治疗。目的:构建基于胃癌组织的类器官模型,探讨其在个性化药物筛查中的应用价值。方法:收集20例胃癌患者术中切除的组织标本,消化分解后与基质胶混合种板,添加含有表皮生长因子和成纤维细胞生长因子10的类器官培养基进行培养。采用苏木精-伊红染色和免疫组化染色对胃癌类器官及原始肿瘤组织进行病理形态学及免疫分子标记同质性验证。通过对卡铂、伊立替康、氟尿嘧啶、奥沙利铂、紫杉醇、表阿霉素等6种药物进行药物敏感性筛查,评估胃癌类器官模型用于药物筛查的可行性。结果与结论:成功培养14例胃癌类器官,类器官的形态及生长特性存在个体性差异,所有类器官均可稳定传代、冻存、复苏。胃癌类器官保留了与原发肿瘤相同的形态学特征及免疫分子表达。6例类器官对6种化疗药物表现出了不同的药物敏感性,初步证实了胃癌类器官作为体外药物筛查模型具有可行性。BACKGROUND:Postoperative adjuvant chemotherapy is a common method for the treatment of gastric cancer,but the curative effect of chemotherapy in different patients varies considerably.A new pre-clinical treatment model is needed to guide personalized drug therapy for patients with gastric cancer.OBJECTIVE:To construct organoid model based on gastric cancer tissue and investigate its application in personalized drug screening.METHODS:The tissue samples of 20 patients with gastric cancer were collected,digested and decomposed,mixed with matrix glue,and cultured with organoid medium containing epidermal growth factor and fibroblast growth factor 10.Hematoxylin-eosin staining and immunohistochemical method were used to verify the homogeneity of pathological morphology and immune molecular markers of gastric cancer organoids and original tumor tissues.The feasibility of the established gastric cancer organoid model for drug screening was evaluated through drug sensitivity screening of six drugs including carboplatin,irinotecan,fluorouracil,oxaliplatin,paclitaxel,and epirubicin.RESULTS AND CONCLUSION:Fourteen organoids of gastric cancer cases were successfully cultured.There were individual differences in morphology and growth characteristics of organoids.All organoids could be stably passed through,froze and resuscitated.Gastric cancer organoids retained the same morphological features and immunomolecular expression as primary tumor tissues.Six organoids showed different drug sensitivities to six chemotherapy drugs,which initially confirmed the feasibility of gastric cancer organoids as a drug screening model in vitro.

关 键 词：类器官 3D培养模型 化疗 个体化治疗 胃癌 药敏 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R656