Developing a Novel Embryo-Larval Zebrafish Xenograft Assay to Prioritize Human Glioblastoma Therapeutics

Leah Christine Wehmas, Robert L. Tanguay, Alex Punnoose, Juliet A. Greenwood

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Glioblastoma is an aggressive brain cancer requiring improved treatments. Existing methods of drug discovery and development require years before new therapeutics become available to patients. Zebrafish xenograft models hold promise for prioritizing drug development. We have developed an embryo-larval zebrafish xenograft assay in which cancer cells are implanted in a brain microenvironment to discover and prioritize compounds that impact glioblastoma proliferation, migration, and invasion. We illustrate the utility of our assay by evaluating the well-studied, phosphatidylinositide 3-kinase inhibitor LY294002 and zinc oxide nanoparticles (ZnO NPs), which demonstrate selective cancer cytotoxicity in cell culture, but the in vivo effectiveness has not been established. Exposures of 3.125-6.25 μM LY294002 significantly decreased proliferation up to 34% with concentration-dependent trends. Exposure to 6.25 μM LY294002 significantly inhibited migration/invasion by ∼27% within the glioblastoma cell mass (0-80 μm) and by ∼32% in the next distance region (81-160 μm). Unexpectedly, ZnO enhanced glioblastoma proliferation by ∼19% and migration/invasion by ∼35% at the periphery of the cell mass (161+ μm); however, dissolution of these NPs make it difficult to discern whether this was a nano or ionic effect. These results demonstrate that we have a short, relevant, and sensitive zebrafish-based assay to aid glioblastoma therapeutic development.

Original languageEnglish (US)
Pages (from-to)317-329
Number of pages13
JournalZebrafish
Volume13
Issue number4
DOIs
StatePublished - Aug 1 2016
Externally publishedYes

Fingerprint

Zebrafish
Glioblastoma
Danio rerio
Heterografts
embryo (animal)
Embryonic Structures
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
therapeutics
assays
brain
zinc oxide
drugs
neoplasms
nanoparticles
cytotoxicity
phosphotransferases (kinases)
cell culture
Zinc Oxide
Therapeutics
cells

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Developmental Biology

Cite this

Developing a Novel Embryo-Larval Zebrafish Xenograft Assay to Prioritize Human Glioblastoma Therapeutics. / Wehmas, Leah Christine; Tanguay, Robert L.; Punnoose, Alex; Greenwood, Juliet A.

In: Zebrafish, Vol. 13, No. 4, 01.08.2016, p. 317-329.

Research output: Contribution to journalArticle

Wehmas, Leah Christine ; Tanguay, Robert L. ; Punnoose, Alex ; Greenwood, Juliet A. / Developing a Novel Embryo-Larval Zebrafish Xenograft Assay to Prioritize Human Glioblastoma Therapeutics. In: Zebrafish. 2016 ; Vol. 13, No. 4. pp. 317-329.
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