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Br J Cancer. 2013 Jun 25;108(12):2485-94. doi: 10.1038/bjc.2013.205. Epub 2013 May 21.

β-blockers increase response to chemotherapy via direct antitumour and anti-angiogenic mechanisms in neuroblastoma.

Author information

1
Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, New South Wales 2031, Australia. e.pasquier@ccia.unsw.edu.au

Abstract

BACKGROUND:

The use of β-blockers for the management of hypertension has been recently associated with significant clinical benefits in cancer patients. Herein, we investigated whether β-blockers could be used in combination with chemotherapy for the treatment of neuroblastoma.

METHODS:

Seven β-blockers were tested for their antiproliferative and anti-angiogenic properties alone, and in combination with chemotherapy in vitro; the most potent drug combinations were evaluated in vivo in the TH-MYCN mouse model of neuroblastoma.

RESULTS:

Three β-blockers (i.e., carvedilol, nebivolol and propranolol) exhibited potent anticancer properties in vitro and interacted synergistically with vincristine, independently of P-glycoprotein expression. β-blockers potentiated the anti-angiogenic, antimitochondrial, antimitotic and ultimately pro-apoptotic effects of vincristine. In vivo, β-blockers alone transiently slowed tumour growth as compared with vehicle only (P<0.01). More importantly, when used in combination, β-blockers significantly increased the tumour regression induced by vincristine (P<0.05). This effect was associated with an increase in tumour angiogenesis inhibition (P<0.001) and ultimately resulted in a four-fold increase in median survival, as compared with vincristine alone (P<0.01).

CONCLUSION:

β-blockers can increase treatment efficacy against neuroblastoma, and their combination with chemotherapy may prove beneficial for the treatment of this disease and other drug-refractory cancers.

PMID:
23695022
PMCID:
PMC3694229
DOI:
10.1038/bjc.2013.205
[Indexed for MEDLINE]
Free PMC Article

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