基因敲除
癌症研究
细胞凋亡
生物
癌细胞
胆碱乙酰转移酶
细胞生长
毒蕈碱乙酰胆碱受体
受体
乙酰胆碱
癌变
细胞周期
癌症
细胞生物学
内分泌学
生物化学
遗传学
作者
Linjun Wang,Xiaofei Zhi,Qun Zhang,Song Wei,Zheng Li,Jianping Zhou,Jian‐Guo Jiang,Yi Zhu,Li Yang,Hao Xu,Zekuan Xu
出处
期刊:Tumor Biology
[SAGE]
日期:2015-09-07
卷期号:37 (2): 2105-2117
被引量:39
标识
DOI:10.1007/s13277-015-4011-0
摘要
The muscarinic receptor M3 is an acetylcholine receptor that regulates the activity of numerous fundamental central and peripheral nervous system functions. Recent studies have identified the activation of the M3 receptor in several cancers; however, the role of M3 in human gastric cancer (GC) remains largely unknown. In this study, we demonstrated that the M3 receptor was overexpressed in human GC tissues and was correlated with the cancer stage and with lymph node metastasis. In vitro, the M3 receptor enhanced the proliferation induced by acetylcholine in human GC cells, whereas the knockdown of M3 by a small hairpin RNA (shRNA) inhibited cell proliferation. Furthermore, M3 knockdown caused G2/M phase cell cycle arrest and induced apoptosis in human GC cells. In vivo, M3 knockdown suppressed tumorigenesis and promoted apoptosis in GC xenografts. In addition, we also detected the secretion of acetylcholine (ACh) by human GC cells and observed the co-expression of the M3 receptor and choline acetyltransferase (ChAT), the enzyme necessary for acetylcholine synthesis, in human GC tissues and cells. Taken together, our findings support an oncogenic role for the M3 receptor in gastric cancer, suggesting that M3 antagonists may serve as potential adjuvants to GC therapies. Further study of the underlying molecular mechanism could also lead to the identification of novel therapeutic targets for improved treatment of GC.
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