PMID- 21157381
OWN - NLM
STAT- MEDLINE
DCOM- 20110307
LR  - 20151119
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Linking)
VI  - 70
IP  - 1
DP  - 2011 Jan
TI  - Block of purinergic P2X7R inhibits tumor growth in a C6 glioma brain tumor animal 
      model.
PG  - 13-22
LID - 10.1097/NEN.0b013e318201d4d4 [doi]
AB  - 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.
FAU - Ryu, Jae K
AU  - Ryu JK
AD  - Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, 
      University of British Columbia, British Columbia, Canada.
FAU - Jantaratnotai, Nattinee
AU  - Jantaratnotai N
FAU - Serrano-Perez, Maria C
AU  - Serrano-Perez MC
FAU - McGeer, Patrick L
AU  - McGeer PL
FAU - McLarnon, James G
AU  - McLarnon JG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Growth Inhibitors)
RN  - 0 (Purinergic P2X Receptor Antagonists)
RN  - 0 (Receptors, Purinergic P2X7)
RN  - 0 (Rosaniline Dyes)
RN  - M1ZRX790SI (coomassie Brilliant Blue)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Brain Neoplasms/drug therapy/*metabolism/pathology
MH  - *Disease Models, Animal
MH  - Drug Delivery Systems/methods
MH  - Gene Expression Regulation/*drug effects
MH  - Glioma/drug therapy/*metabolism/pathology
MH  - Growth Inhibitors/administration & dosage/*pharmacology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Purinergic P2X Receptor Antagonists/administration & dosage/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Receptors, Purinergic P2X7/biosynthesis/genetics
MH  - Rosaniline Dyes/administration & dosage/pharmacology
MH  - Tumor Cells, Cultured
EDAT- 2010/12/16 06:00
MHDA- 2011/03/08 06:00
CRDT- 2010/12/16 06:00
PHST- 2010/12/16 06:00 [entrez]
PHST- 2010/12/16 06:00 [pubmed]
PHST- 2011/03/08 06:00 [medline]
AID - 10.1097/NEN.0b013e318201d4d4 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2011 Jan;70(1):13-22. doi: 
      10.1097/NEN.0b013e318201d4d4.