ABSTRACT
As a model organism, zebrafish have many advantages over other animal models and is suitable for studies on establishment of human disease model and mechanism.In zebrafish, there are two phases of endocrine formation during early development, which are directed by concomitant activity of many signaling pathways.Zebrafish pancreas possess similar cell structure with that of other animals, which can express various endocrine hormones including insulin.The main organs required for metabolic control, such as the pancreas, islet, and insulin sensitive tissue (muscle, liver) are conserved in zebrafish, and the mechanisms of glucose regulation in zebrafish is similar to that seen in mammalian models.These render it an excellent model to study glucose metabolism.Hyperglycemia in zebrafish model can be induced by administration of the diabetogenic drug, streptozotocin (STZ), alternatively immersion of the fish in glucose solution and water, or disturbing of signaling pathways associated with glucose metabolism.Glucose levels in adult zebrafish blood or embryo tissue and phenotype of retinal cell layers or retinal vasculature are the commonly used measurement organs in zebrafish diabetic models.
ABSTRACT
Aim To investigate the modeling of breast cancer in zebrafish embryos and its related protein expression. Methods 48hpf wild type AB/ TG(Transgenic) zebrafishs were micro-in-jected with breast cancer cell line: MCF-7,T-47D, MDA-MB-231 respectively, the relationship between the number of tumor and model application was investigated, and the number of sub-intestinal veins(SIVs) was detected under confocal microscope, as well as the metastasis of tumor cells in embryos; then the ze-brafish xenografts of MB-231 were co-cultured with tofacitinib/ptk787 for 48 h, optical density(OD) of the cell survival and subintestinal veins(SIVs) were evaluated under confocal micro-scope, and Western blot(WB) analysis was used to test micro-circumstances related protein. Results When the number of in-oculated cells was more than 200 per embryo, xenograft model rate woule be more than 0. 90;MB-231 xenografts showed metas-tasis feature in zebrafish, which could be inhibited by tofacitinib (P < 0. 01), while the number of xenograft MB-231 cells was reduced significantly(P < 0. 01); in another zebrafish xenografts SIVs assay, the tumor could promote the proliferation of SIVs, and 4 mg·L - 1 PTK787 showed inhibiton effect( P < 0. 01). Western blot showed 4d T-47D xenograft zebrafish got more HER2 expression than AB embryos; VEGFa expression in ze-brafish MB-231 model group was higher, and model zebrafish P53 expressi was higher after treated by tofacitinib. Conclusion A zebrafish xenograft model of human brest cancer can be es-tablished, which demonstrates applicability for screening com-pounds in drug discovery studies.
ABSTRACT
Aim To investigate the anti-angiogenesis and anti-xenograftes of UA in zebrafish larvaes. Meth-ods 24 hour post-fertilization ( hpf ) TG zebrafish was treated with different concentration of UA for 24h, and the number of intersegmental vessels( IVS) were detec-ted under fluorescent microscope respectively;then the models of AB/TG zebrafish xenografts were established by be micro-injected with SMMC-7721 or HT-29 cell at 48hpf respectively, and after cocultured with UA for 48h, optical density (OD) of the SMMC-7721 cell and subintestinal veins ( SIVs) induced by HT-29 were e-valuated under confocal microscope. Results ISV as-say showed that UA could cause IVS missing or disap-perance, inhibition ratio reaching 20. 25% and 26. 65%. UA blocked the spread of SMMC-7721 cells in zebrafish and OD value,and inhibition ratios at three concentrations were 38. 01%, 54. 69%, 61. 88%, re-spectively; in another SIVs assay induced by xeno-grafts, UA at concentration 10 and 15mg·L-1 showed that SIVs were inhibited (P<0. 01) obviously. Con-clusion UA could inhibit the angiogenesis and the growth of SMMC-7721/HT-29 xenografts,and the anti-tumor mechanism may be related with VEGFR2 expres-sion.
ABSTRACT
Aim To study the cardiotoxicity of celastrol to zebrafish embryo.Method 48 h post-fertilization zebrafish embryos were used as model for analysis of heart toxicity and were treated with various concentrations of celastrol.6,12,24 h after treatment morphological and functional changes of embryos hearts were observed.Results Cardiotoxicity was not found in embryos during 24 h treatment with 1 ?mol?L-1 concentration of celastrol.Toxic symptoms of embryos were caused by 2,3,4 ?mol?L-1 concentrations of celastrol with appearance of heart linearization,heart membrane hemorrhage and hemocytes accumulation in cardiac region.Moreover,heart rate decreased significantly with increase of concentration and prolongation of treatment.The EC50(24 h)of decrease of heart rate was about 1.78 ?mol?L-1.Conclusion Celastrol is cardiotoxic to zebrafish embryo.