We examined the expression and pharmacological modulation of the
purinergic receptor P2X7R in a C6
glioma model. Intrastriatal injection of C6 cells induced a time-dependent growth of
tumor; at 2 weeks postinjection immunohistochemical analysis demonstrated higher levels of P2X7R in
glioma-injected versus control vehicle-injected brains. P2X7R immunoreactivity colocalized with
tumor cells and microglia, but not endogenous astrocytes.
Intravenous administration of the P2X7R antagonist
brilliant blue G (BBG) inhibited
tumor growth in a spatially dependent manner from the C6 injection site. Treatment with BBG reduced
tumor volume by 52% versus that in controls. Double immunostaining indicated that BBG treatment did not alter microgliosis,
astrogliosis, or vasculature vessels in C6-injected animals. In vitro, BBG reduced the expression of P2X7R and
glioma chemotaxis induced by the P2X7R
ligand, 2',3'-O-(4-benzoyl-benzoyl)adenosine
triphosphate (
BzATP). Immunohistochemical staining of human
glioblastoma tissue samples demonstrated greater expression of P2X7R compared to control nontumor samples. These results suggest that the efficacy of BBG in inhibiting
tumor growth is primarily mediated by direct actions of the compound on P2X7R in
glioma cells and that pharmacological inhibition of this
purinergic receptor might serve as a strategy to slow the progression of
brain tumors.