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Br J Cancer. 2014 Dec 9;111(12):2275-86. doi: 10.1038/bjc.2014.529. Epub 2014 Nov 6.

Interrogation of gossypol therapy in glioblastoma implementing cell line and patient-derived tumour models.

Author information

1
Department of Physiology and Medical Physics and Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
2
1] Molecular Therapeutics for Cancer Ireland, Dublin City University, Dublin 9, Ireland [2] All Ireland Cooperative Oncology Research Group, Dublin 2, Ireland.
3
1] UCD School of Veterinary Medicine, University College Dublin, Dublin 4, Ireland [2] Ross School of Veterinary Medicine, Basseterre, St Kitts, West Indies.
4
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
5
UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin 4, Ireland.
6
Department of Biomedicine, University of Bergen, Bergen, Norway.
7
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
8
PHS Department of Epidemiology and Public Health Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
9
1] Department of Physiology and Medical Physics and Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland [2] UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin 4, Ireland.

Abstract

BACKGROUND:

Glioblastoma (GBM), being a highly vascularised and locally invasive tumour, is an attractive target for anti-angiogenic and anti-invasive therapies. The GBM/endothelial cell response to gossypol/temozolomide (TMZ) treatment was investigated with a particular aim to assess treatment effects on cancer hallmarks.

METHODS:

Cell viability, endothelial tube formation and GBM tumour cell invasion were variously assessed following combined treatment in vitro. The U87MG-luc2 subcutaneous xenograft model was used to investigate therapeutic response in vivo. Viable tumour response to treatment was interrogated using immunohistochemistry. Combined treatment protocols were also tested in primary GBM patient-derived cultures.

RESULTS:

An endothelial/GBM cell viability inhibitory effect, as well as an anti-angiogenic and anti-invasive response, to combined treatment have been demonstrated in vitro. A significantly greater anti-proliferative (P=0.020, P=0.030), anti-angiogenic (P=0.040, P<0.0001) and pro-apoptotic (P=0.0083, P=0.0149) response was observed when combined treatment was compared with single gossypol/TMZ treatment response, respectively. GBM cell line and patient-specific response to gossypol/TMZ treatment was observed.

CONCLUSIONS:

Our results indicate that response to a combined gossypol/TMZ treatment is related to inhibition of tumour-associated angiogenesis, invasion and proliferation and warrants further investigation as a novel targeted GBM treatment strategy.

PMID:
25375271
PMCID:
PMC4264441
DOI:
10.1038/bjc.2014.529
[Indexed for MEDLINE]
Free PMC Article

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