毛花素
癌症研究
基因沉默
胰腺癌
流式细胞术
生物
下调和上调
转化生长因子
癌症
医学
细胞生物学
免疫学
内科学
内分泌学
大豆黄酮
生物化学
芒柄花素
染料木素
基因
作者
Wenqing Chen,Zhu Zhang,Ken Kin Lam Yung,Joshua Ka-Shun Ko
出处
期刊:PubMed
日期:2022-01-01
卷期号:12 (7): 3242-3258
被引量:4
摘要
Pancreatic ductal adenocarcinoma (PDAC) is a prominent type of pancreatic cancer. We have recently unveiled that the anti-tumor adjuvant calycosin concurrently possesses growth-inhibitory and pro-metastatic potential in PDAC development by regulating transforming growth factor β (TGF-β), which plays dual roles as both tumor suppressor and tumor promoter. Hence, we are interested to explore if the pro-metastatic property of the drug could be attenuated for effective treatment of PDAC. Through network pharmacology, MUC1 had been identified as the most common drug target of herbal Astragalus constituents (including calycosin) in treating PDAC. Following MUC1 gene silencing, the drug effects of calycosin on migratory activity, growth and metabolic regulation of PDAC cells were assessed by using immunofluorescence microscopy, quantitative real-time polymerase chain reaction (qRT-PCR), Western immunoblotting, co-immunoprecipitation (Co-IP), wound healing assay and flow cytometry, respectively. Through in vivo experiments, we further validated the working relationship between MUC1 and TGF-β. Results have elucidated that MUC1 gene suppression could switch off the migratory and pro-metastatic drive of calycosin while retaining its growth-inhibitory power by inducing apoptosis and cell cycle arrest, as well as facilitating autophagy and metabolic regulation. The underlying mechanism involves downregulation of TGF-β that acts via modulation of AMP-activated protein kinase (AMPK), Sirtuin 1 (Sirt1) and fibroblast growth factor 21 (FGF21) signaling. These findings have provided new insights in the safe and target-specific treatment of PDAC.
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