ZFIN ID: ZDB-PUB-171101-6
Identify a Blood-Brain Barrier Penetrating Drug-TNB using Zebrafish Orthotopic Glioblastoma Xenograft Model
Zeng, A., Ye, T., Cao, D., Huang, X., Yang, Y., Chen, X., Xie, Y., Yao, S., Zhao, C.
Date: 2017
Source: Scientific Reports   7: 14372 (Journal)
Registered Authors: Yao, Shaohua
Keywords: none
MeSH Terms:
  • Animals
  • Blood-Brain Barrier/drug effects*
  • Blood-Brain Barrier/pathology
  • Brain Neoplasms/pathology
  • Cell Line
  • Cell Line, Tumor
  • Disease Models, Animal
  • Disease Progression
  • Drug Delivery Systems
  • Glioblastoma/drug therapy*
  • Glioblastoma/pathology
  • Humans
  • Small Molecule Libraries/pharmacology*
  • Transplantation, Heterologous
  • Xenograft Model Antitumor Assays
  • Zebrafish
PubMed: 29085081 Full text @ Sci. Rep.
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ABSTRACT
The blood-brain barrier (BBB) is necessary for maintaining brain homeostasis, but it also represents a major challenge for drug delivery to the brain tumors. A suitable in vivo Glioblastoma Multiforme (GBM) model is needed for efficient testing of BBB crossable pharmaceuticals. In this study, we firstly confirmed the BBB functionality in 3dpf zebrafish embryos by Lucifer Yellow, Evans Blue and DAPI microinjection. We then transplanted human GBM tumor cells into the zebrafish brain, in which implanted GBM cells (U87 and U251) were highly mitotic and invasive, mimicking their malignancy features in rodents' brain. Interestingly, we found that, although extensive endothelial proliferation and vessel dilation were observed in GBM xenografts, the BBB was still not disturbed. Next, using the zebrafish orthotopic GBM xenograft model as an in vivo visual readout, we successfully identified a promising small compound named TNB, which could efficiently cross the zebrafish BBB and inhibit the progression of orthotopic GBM xenografts. These results indicate that TNB is a promising BBB crossable GBM drug worth to be further characterized in human BBB setting, also suggest the zebrafish orthotopic GBM model as an efficient visual readout for the BBB penetrating anti-GBM drugs.
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