首页|微乳头型肺腺癌类器官的构建及其靶向药物的筛选

微乳头型肺腺癌类器官的构建及其靶向药物的筛选

Construction of micropapillary lung adenocarcinoma organoids and screening of targeted drugs

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目的 建立微乳头型肺腺癌类器官的培养方法,并开展靶向药物的筛选.方法 自确诊为微乳头型肺腺癌患者手术组织样本中提取和培养原代肺癌类器官,动态观察和记录肺癌类器官生长情况;苏木精-伊红(HE)染色法及免疫组化染色法比较肺癌类器官与亲本组织间肿瘤细胞形态及蛋白表达特征;实时荧光定量聚核酶链反应检测肺癌亲本组织和类器官中基因突变情况;基于基因检测结果挑选靶向药物并验证其体外抑瘤效果.结果 成功从微乳头型肺腺癌组织中培养出类球形肿瘤类器官,可传代至少3代.HE染色结果可见类器官中肿瘤细胞形态与亲本组织细胞基本一致;免疫组化染色结果显示肺癌类器官与亲本组织中各基因的蛋白表达水平大致相同;基因突变分析结果显示,肺癌亲本组织和类器官的突变基因结果一致,均体现为原癌基因酪氨酸蛋白激酶受体Ret(RET)融合突变.基于肺癌类器官的靶向药物筛选结果显示,凡德他尼的体外抑瘤效果最佳.结论 基于微乳头型肺腺癌类器官的药筛实验可在短时间内筛选出高效靶向药物,可使微乳头型肺腺癌患者从中获益.
Objective To establish a culture method for micropapillary lung adenocarcinoma organoids and conduct targeted drug screening.Methods Organoids were extracted and cultured from a surgical tissue sample of a patient diagnosed with micropapillary lung adenocarcinoma,and the growth of lung cancer organoids was observed and recorded dynamically.The morphological and gene expression characteristics of tumor cells between lung cancer organoids and parental tissue were compared using hematoxylin eosin(HE)staining and immunohistochemical methods.Real time fluorescence quantitative polynucleotide chain reaction(qRT-PCR)method was used to detect gene mutations in lung cancer parental tissue and organoids.Finally,based on results of genetic testing,targeted drugs were selected and their therapeutic effects were verified.Results We have successfully cultured spherical organoids from micropapillary lung adenocarcinoma tissue,which can be passaged for at least 3 generations.HE staining results showed that the morphology of tumor cells in organoids was roughly consistent with that of parental tissue.The immunohistochemical results showed that the protein expression levels of various genes in lung cancer organoids and parental tissue were roughly the same.Results of gene mutation analysis showed that the mutated genes in lung cancer parental tissue and organoids were consistent,both reflecting RET fusion.The screening results of targeted drugs based on lung cancer organoids showed that vandertinib had the best anti-tumor effect in vitro.Conclusion Drug screening experiments based on micropapillary lung adenocarcinoma organoids can screen highly efficient targeted drugs in a short period of time,which may benefit patients with micropapillary lung adenocarcinoma.

adenocarcinoma of lungorganoidsdrug screening assays,antitumortargeting preparationvandetani

姜忠敏、张春艳、刘敏、郑洁、李艳霞、仁青措、孟纬、刘晓智

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天津市第五中心医院病理科(邮编 300450)

天津市早产儿器官发育表观遗传重点实验室

天津市第五中心医院普通外科

青海黄南藏族自治州人民医院高原特色医学研究所

青海黄南藏族自治州人民医院传染科

青海黄南藏族自治州人民医院骨科

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肺腺癌 类器官 药物筛选试验,抗肿瘤 靶向制剂 凡德他尼

天津市科技计划天津市自然科学基金天津市卫生健康科技项目天津市卫生健康科技项目天津市卫生健康科技项目天津市卫生健康委(天津市中医药局)中医中西医结合科研课题天津市医学重点学科(专科)建设项目天津市医学重点学科(专科)建设项目天津市援建同仁市民生科技项目天津市卫生健康委中医中西医结合科研课题

22ZYQYSY0003021JCZDJC01270TJWJ2022XK043TJWJ2023MS053TJWJ2023QN1032021061TJYXZDXK-062BTJYXZDXK-079D2023062

2024

10.11958/20231326

天津医药
天津市医学科学技术信息研究所

天津医药

CSTPCD
影响因子：1.107
ISSN：0253-9896
年,卷(期)：2024.52(1)
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