The Effect Of Muscarinic M1 Receptors On The Invasion And Migration Of Prostate Cancer And The Underlying Mechanisms

Objective: The intension of this study was to investigate the influence of muscarinic M1 receptor on the invasion and migration of prostate cancer and the underlying mechanisms.Methods: Immunohistochemical staining was used to detect the expression of muscarinic M1 receptor in human prostate cancer tissues,and the relationship between the expression of M1 receptors and clinicopathological features of prostate cancer was analysed.To assess the role of muscarinic M1 receptor in the invasion and migration of cancer cells,PC-3?LNCaP?and A549 cells were treated with cholinergic muscarinic receptor subtype 1(Chrm1)antagonist pirenzepine or agonist carbachol.The invasion and migration of the three cancer cells were detected by Transwell assays.Treatment of prostate cancer PC-3 cells with muscarinic receptor antagonist or agonist for different times,the expression level of Shh?Ptch1?Gli1 were detected by western blotting analysis.The PC-3 cells were treated by pirenzepine for different concentrations,and the mRNA expression of Shh?Ptch1?Gli1 were detected by RT-PCR assays.Results: The expression of M1 receptors was higher in the early stage human prostate cancer tissues than in late stage prostate cancer tissues.In addition,Chrm1 antagonist pirenzepine inhibited the migration and invasion of PC-3,LNCaP and A549 cells,agonist carbachol promoted the migration and invasion of these three cell lines.Cholinergic signaling might be relayed by hedgehog signaling.