Inhibitory effect of sinomenine on lung cancer cells via negative regulation of α7 nicotinic acetylcholine receptor

• DOI: 10.1002/jlb.6ma0720-344rrr
• Publication Date: 2020-07-29T23:36:52Z
• Authors: Shasha Bai; Wenhao Wen; Xuenan Hou; Jiexiu Wu; Lang Yi; Yingkun Zhi; Yanjun Lv; Xiaoqin Tan; Liang Liu; Peixun Wang; Hua Zhou; Yan Dong
• Keywords: Sinomenine; Methyllycaconitine

Abstract Lung cancer is the leading cause of deaths worldwide, with a high morbidity and less than 20% survival rate. Therefore, new treatment strategies drugs are needed to reduce mortality patients lung cancer. α7 nicotinic acetylcholine receptor (α7 nAChR), as nicotine its metabolites, potential target for treatment. Our previous studies revealed that sinomenine plays anti-inflammation roles via nAChR down-regulates expression this receptor, thus increasing inflammatory response. Hence, possibly natural ligand receptor. In present study, effects on A549 cells tumor-bearing mice were determined investigate whether alkaloid has an inhibitory effect nAChR. CCK-8 assay, wound-healing test, flow cytometry performed cell proliferation, migration, apoptosis analysis in vitro, respectively. Xenograft used evaluate vivo. Results showed decreased proliferation migration abilities but increased percentage apoptotic cells. Tumor volume was significantly reduced after compared vehicle group (p < 0.05). Furthermore, abolished by antagonist mecamylamine allosteric modulator PNU-120596, no change occurred when pretreated muscarinic atropine. Meanwhile, suppressed vitro vivo, well related signaling molecules pERK1/2 ERK1/2 transcription factors TTF-1 SP-1. By contrast, up-regulated another factor, Egr-1. These restricted PNU not suggested can inhibit negative feedback mode.