Baicalein inhibits acinar‐to‐ductal metaplasia of pancreatic acinal cell AR42J via improving the inflammatory microenvironment

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Recent research has demonstrated that chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due to acinar‐to‐ductal metaplasia (ADM). Baicalein has been shown to exert anti‐inflammatory and anti‐t...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cellular physiology 2018-08, Vol.233 (8), p.5747-5755
Main Authors: Pu, Wei‐Ling, Luo, Ying‐Ying, Bai, Ru‐Yu, Guo, Ao‐Wei, Zhou, Kun, Zhang, Yun‐Sha, Miao, Lin, Rüegg, Curzio, Hottiger, Micheal O., Gao, Xiu‐Mei, Sun, Li‐Kang
Format: Article
Language:English
Subjects:
Acinar cells
acinar‐to‐ductal metaplasia
Activation
Adenocarcinoma
baicalein
Cytokeratin
Cytokines
Gene expression
Inflammation
inflammatory microenvironment
Inflammatory response
Lipopolysaccharides
Macrophages
Metaplasia
NF‐κB
Nitric oxide
Notch‐1
Pancreas
Pancreatic cancer
Pancreatitis
Phenotypes
Tumor necrosis factor-α
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Recent research has demonstrated that chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due to acinar‐to‐ductal metaplasia (ADM). Baicalein has been shown to exert anti‐inflammatory and anti‐tumor effects for CP or PDAC, respectively. The aim of our study was to investigate the effect of baicalein, and the putative underlying mechanism, on inflammatory cytokines‐induced ADM of rat pancreatic acinar cell line AR42J. To investigate ADM and baicalein effects in vitro, AR42J were treated with recombinant rat Tumor Necrosis Factor alpha (rTNFα) with or without baicalein for 5 days. Results showed that rTNFα‐induced AR42J cells switched their phenotype from dominantly amylase‐positive acinar cells to dominantly cytokeratin 19‐positive ductal cells. Moreover, expression of the transcripts for TNFα or Hes‐1, a Notch target, was up‐regulated in these cells. Interestingly, baicalein reduced the population of ADM as well as cytokines gene expression but not Hes‐1. Baicalein inhibited NF‐κB activation induced by rTNFα in AR42J, but no effect on Notch 1activation. Moreover, baicalein suppressed the secretion of TNFα and Nitric Oxide (NO) in macrophages stimulated with LPS and further inhibited ADM of conditional medium‐treated AR42J cells. Baicalein also suppressed the inflammatory response of LPS‐activated macrophages, thereby inhibited ADM of AR42J by altering their microenvironment. Taken together, our study indicates that baicalein reduces rTNFα‐induced ADM of AR42J cells by inhibiting NF‐κB activation. It also sheds new light on Chinese material medica therapy of pancreatitis and thereby prevention of PDAC. Chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due to acinar‐to‐ductal metaplasia (ADM). Baicalein, an active compound isolated from the roots of Scutellaria baicalensis Georgi, exert anti‐inflammatory and anti‐tumor effects for CP or PDAC. Our research showed that baicalein could suppress the acinar‐to ductal metaplasia (ADM) of pancreatic acinar cell AR42J via inhibition of NF‐κB activation. Furthermore, Baicalein also suppressed the inflammatory response of LPS‐activated macrophages, thereby inhibited ADM of AR42J through an altered microenvironment. Together, our study may provide new light on Chinese material medica therapy of pancreatitis and thereby prevention of PDAC.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.26293