Choline and nicotine increase glioblastoma cell proliferation by binding and activating ?7- and ?9- containing nicotinic receptors

Glioblastomas (GBMs), the most frequent and aggressive human primary brain tumours, have altered cell metabolism, one of strongest indicators malignancy is an increase in choline compounds. Choline also a selective agonist some neuronal nicotinic acetylcholine receptor (nAChR) subtypes. As little known concerning expression nAChR glioblastoma cells, we analysed U87MG grade-IV astrocytoma line GBM5 temozolomide-resistant cells selected from cancer stem cell-enriched culture, molecularly, pharmacologically functionally which subtypes are expressed and,whether nicotine can affect GBM proliferation. We found that express similar subtypes, their proliferation rate activate anti-apoptotic AKT pro-proliferative ERK pathways. These effects blocked by presence non-cell-permeable peptide antagonists for ?7- ?9-containing receptors. siRNA-mediated silencing ?7 or ?9 subunit selectively prevents on Our findings indicate signalling pathways involved these mediated nAChRs. This suggests receptors may contribute to behaviour this tumor new therapeutic strategies against high-grade tumours.