P2X7 receptor antagonism inhibits tumour growth in human high-grade gliomas
| Autor: | Sinali O. Seneviratne, Kate Drummond, Liyen Katrina Kan, Mastura Monif, David A. Williams, Terence J. O'Brien |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Purinergic P2X Receptor Antagonists Cell Adamantane 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Downregulation and upregulation Glioma Cell Line Tumor medicine Rosaniline Dyes Tumor Microenvironment Humans Molecular Biology Cell Proliferation Tumor microenvironment Temozolomide Microscopy Confocal Microglia Cell growth Chemistry Brain Neoplasms Cell Biology medicine.disease Highlights 030104 developmental biology medicine.anatomical_structure Cell culture Cancer research Aminoquinolines Receptors Purinergic P2X7 030217 neurology & neurosurgery medicine.drug Signal Transduction |
| Zdroj: | Purinergic Signal |
| ISSN: | 1573-9546 |
| Popis: | Gliomas, the most common primary brain cancer, are highly infiltrative and extremely difficult to treat. Despite advancements, current treatment is limited, with patients surviving for a median of 14-15 months post-diagnosis. Previous research has demonstrated the upregulation of a purinergic receptor, P2X7R, in human gliomas. P2X7R is expressed on both glioma cells and microglia within the glioma microenvironment. It is hypothesized that P2X7R contributes to tumour growth and proliferation via immune-mediated mechanisms involving tumour cells and surrounding microglia. We sought to elucidate the role of P2X7R in a human glioblastoma cell line (U251) and on surgically resected human glioma samples. We treated U251 and human glioma cultures for 72 h with P2X7R antagonists, Brilliant Blue G (BBG), oxidized ATP (oATP) and AZ10606120. Cell counting via fluorescence confocal microscopy was conducted to assess tumour proliferation. We observed no significant reductions in tumour cell numbers following P2X7R antagonism with BBG (20 μM) and oATP (250 μM) in both U251 cells and human glioma samples. Interestingly, there was a significant reduction in tumour cell number in both U251 cells (p = 0.0156) and human glioma samples (p = 0.0476) treated with varying concentrations of AZ10606120. When compared with the conventional chemotherapeutic agent, temozolomide, AZ10606120 was also found to more effectively inhibit tumour proliferation in U251 cells (p |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink