Establishment of Patient-Derived Xenograft (PDX) Zebrafish Model of Multiple Myeloma and Its Application in Drug Screening / 中国实验血液学杂志

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.

Effect of indirubin-3'-monoxime on proliferation and apoptosis of human HT-29 cells / 中国癌症杂志

Background and purpose: In recent years indirubin-3'-monoxime has been found to be capable of inhibiting some cell proliferation in vitro and in vivo studies, but human colon cancer HT-29 cells, therefore the purpose in this paper was to study the effect of indirubin-3'-monoxime on proliferation and apoptosis of HT-29 cells and its associated mechanism. Methods: HT-29 cells were treated with indirubin-3'-monoxime. The proliferative status of cells was measured by methabenzthiazuron (MTT) assay, flow cytometry (FCM) was used to measure the apoptosis rate. RT-PCR was used to measure the transcription of apoptosis suppressor gene bcl-2, survivin and apoptosis promoting gene Bar. Results: Indimbin-3'-monoxime inhibited growth of HT-29 cells in a dose-dependent and time-dependent manner (F=11.25, P<0.01). The apoptosis rate increased after the treatment by indirubin-3'-monoxime at 10 μmol/L. There were significant differences between different time groups (F=195.25, P<0.01). The transcription of survivin (F=78.75, P<0.01) and Bax (F=87.61, P<0.01) mRNA in HT-29 cells were increased; the transcription of bcl-2 was significantly decreased (F=95.82, P<0.01). Conclusion: Indirubin-3'-monoxime has obviously inhibited proliferation and induce apoptosis of colon cancer HT-29 cells, its mechanism may be related to decrease the bcl-2/Bax ratio.