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(P<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.
题目: 多发性骨髓瘤原代细胞斑马鱼模型的建立 及其在药物筛选中的应用.
目的: 应用斑马鱼建立多发性骨髓瘤（MM）患者原代肿瘤细胞来源的人源肿瘤异种移植模型（MM-PDX），利用该模型对候选药物靛玉红-3′-单肟（I3MO）的抗骨髓瘤活性进行药效学评价.
方法: 取受精后2 d的斑马鱼胚胎进行荧光标记的MM患者原代肿瘤细胞移植，细胞注射后0、16和24 h，观察MM患者原代肿瘤细胞在斑马鱼体内生存，将肿瘤细胞移植后的斑马鱼胚胎随机分为对照、BTZ治疗、I3MO治疗共3组，在药物BTZ、I3MO处理前和处理24 h后，通过荧光显微镜观察斑马鱼体内荧光区域面积反映MM患者原代肿瘤细胞存活情况并验证.
结果: MM患者原代肿瘤细胞可在斑马鱼体内存活，MM-PDX构建成功。与对照组相比，BTZ和I3MO药物干预后斑马鱼体内荧光区域的面积均显著降低（P<0.05），BTZ、I3MO显著抑制MM细胞在斑马鱼体内的生存.
结论: 成功建立了原代MM患者肿瘤细胞来源的斑马鱼模型MM-PDX，应用此模型可作为抗MM药物筛选的工具.
Keywords: Bortezomib; indirubin-3’-monoxime; multiple myeloma; patient-derived tumor xenograft model; zebrafish.