[多发性骨髓瘤患者来源异种移植（PDX）斑马鱼模型的建立及其在药物筛选中的应用]
[Establishment of Patient-Derived Xenograft (PDX) Zebrafish Model of Multiple Myeloma and Its Application in Drug Screening].
作者信息
Yu Zhen, Li Ying, Wang Ke-Fei, Wang Lu, Hao Mu
机构信息
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China,E-mail:
出版信息
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Dec;31(6):1745-1749. doi: 10.19746/j.cnki.issn.1009-2137.2023.06.022.
OBJECTIVE
To establish a MM patient-derived tumor xenograft model (MM-PDX) in zebrafish, and to evaluate the anti-myeloma activity of indirubin-3'-monoxime(I3MO) using this model.
METHODS
Zebrafish embryos 2 days after fertilization were transplanted with fluorescence labeled myeloma primary tumor cells, the survival of primary tumor cells in zebrafish was observed at 0,16 and 24 hours after cell injection. The zebrafish embryos after tumor cell transplantation were randomly divided into control group, BTZ treatment and I3MO treatment group. Before and 24 hours after treatment with BTZ and I3MO, the positive area with calcein or Dil in zebrafish were observed under fluorescence microscope to reflect the survival of tumor cells, and it was verified.
RESULTS
MM patient derived tumor cells survived in zebrafish. The construction of MM-PDX was successful. Compared with control group, the fluo- rescence area of the BTZ and I3MO treatment groups in zebrafish were significantly decreased(<0.05), and BTZ and I3MO significantly inhibited the survival of MM cells in zebrafish.
CONCLUSION
MM-PDX model was successfully established. Zebrafish model derived from tumor cells of MM patients can be used as a tool for drug screening of MM.
目的
在斑马鱼中建立多发性骨髓瘤患者来源的肿瘤异种移植模型（MM-PDX），并使用该模型评估靛玉红-3'-单肟（I3MO）的抗骨髓瘤活性。
方法
将荧光标记的骨髓瘤原代肿瘤细胞移植到受精后2天的斑马鱼胚胎中，在细胞注射后0、16和24小时观察原代肿瘤细胞在斑马鱼中的存活情况。将移植肿瘤细胞后的斑马鱼胚胎随机分为对照组、硼替佐米（BTZ）治疗组和I3MO治疗组。在BTZ和I3MO治疗前及治疗后24小时，在荧光显微镜下观察斑马鱼中钙黄绿素或Dil的阳性区域以反映肿瘤细胞的存活情况，并进行验证。
结果
多发性骨髓瘤患者来源的肿瘤细胞在斑马鱼中存活。MM-PDX构建成功。与对照组相比，斑马鱼中BTZ和I3MO治疗组的荧光面积显著降低（<0.05），BTZ和I3MO显著抑制了斑马鱼中骨髓瘤细胞的存活。
结论
成功建立了MM-PDX模型。源自多发性骨髓瘤患者肿瘤细胞的斑马鱼模型可作为多发性骨髓瘤药物筛选的工具。
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