PURPOSE: Muscarinic cholinergic receptors (MR) have been implicated to be overexpressed in lung cancer, and antagonists of MR have been proved to abrogate the growth of lung cancer cells. Aclidinium Bromide, identified as a muscarinic antagonist targeting muscarinic cholinergic receptor 3 (M3R) in the lung, is proposed as a maintenance treatment in patients with chronic obstructive pulmonary disease (COPD). In this study, we intended to investigate whether the Aclidinium Bromide held potential effects on lung cancer cells behaviors. METHODS: Human lung cancer A549 cell line was used and treated with Aclidinium Bromide. CCK-8 was used to assess cell proliferation, transwell was used to test cell invasion and Western blot assay determined the affected pathways. Apoptosis was detected by flow cytometry using Annexin V-FITC/Propidium iodide (PI)staining. RESULTS: The expression of Bcl-2 declined, and Bax and Caspase 3 increased in A549 cells treated with Aclidinium Bromide. Additionally, Aclidinium Bromide suppressed the PI3K/AKT signaling pathway in lung cancer A549 cells. CCK-8 showed that Aclidinium Bromide could suppress the growth of lung cancer cells A549. By transwell assay, Aclidinium Bromide displayed significant inhibition of cell invasion and migration capabilities. Aclidinium Bromide could induce cell apoptosis, which was detected by flow cytometry and western blot analysis of apoptosis-related markers levels. CONCLUSION: Our results reveals that Aclidinium Bromide behaves as a novel M3R antagonist, and may inhibit lung cancer cell growth by regulating the PI3K/AKT signaling pathway, which sheds some light on that it might be a potential therapeutic agent for lung cancer.
PURPOSE: Muscarinic cholinergic receptors (MR) have been implicated to be overexpressed in lung cancer, and antagonists of MR have been proved to abrogate the growth of lung cancer cells. Aclidinium Bromide, identified as a muscarinic antagonist targeting muscarinic cholinergic receptor 3 (M3R) in the lung, is proposed as a maintenance treatment in patients with chronic obstructive pulmonary disease (COPD). In this study, we intended to investigate whether the Aclidinium Bromide held potential effects on lung cancer cells behaviors. METHODS:Humanlung cancer A549 cell line was used and treated with Aclidinium Bromide. CCK-8 was used to assess cell proliferation, transwell was used to test cell invasion and Western blot assay determined the affected pathways. Apoptosis was detected by flow cytometry using Annexin V-FITC/Propidium iodide (PI)staining. RESULTS: The expression of Bcl-2 declined, and Bax and Caspase 3 increased in A549 cells treated with Aclidinium Bromide. Additionally, Aclidinium Bromide suppressed the PI3K/AKT signaling pathway in lung cancer A549 cells. CCK-8 showed that Aclidinium Bromide could suppress the growth of lung cancer cells A549. By transwell assay, Aclidinium Bromide displayed significant inhibition of cell invasion and migration capabilities. Aclidinium Bromide could induce cell apoptosis, which was detected by flow cytometry and western blot analysis of apoptosis-related markers levels. CONCLUSION: Our results reveals that Aclidinium Bromide behaves as a novel M3R antagonist, and may inhibit lung cancer cell growth by regulating the PI3K/AKT signaling pathway, which sheds some light on that it might be a potential therapeutic agent for lung cancer.