The protective role of sphingosine-1-phosphate against the action of the vascular disrupting agent combretastatin A-4 3-O-phosphate.

ABSTRACT: Solid tumours vary in sensitivity to the vascular disrupting agent combretastatin A-4 3-O-phosphate (CA4P), but underlying factors are poorly understood. The signaling sphingolipid, sphingosine-1-phosphate (S1P), promotes vascular barrier integrity by promoting assembly of VE-cadherin/β-catenin complexes. We tested the hypothesis that tumour pre-treatment with S1P would render tumours less susceptible to CA4P. S1P (1μM) pretreatment attenuated an increase in endothelial cell (HUVEC) monolayer permeability induced by 10μM CA4P. Intravenously administered S1P (8mg/kg/hr for 20 minutes then 2mg/kg/hr for 40 minutes), reduced CA4P-induced (30mg/kg) blood flow shut-down in fibrosarcoma tumours in SCID mice (n≥7 per group), as measured by tumour retention of an intravenously administered

SUBMITTER: Shepherd J 

PROVIDER: S-EPMC5707050 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature