-
Tytuł:
-
Secretory Phospholipase A 2 Inhibition Attenuates Adhesive Properties of Esophageal Barrett's Cells.
-
Autorzy:
-
Gergen AK; University of Colorado School of Medicine, Department of Surgery, Division of Cardiothoracic Surgery, Aurora, Colorado. Electronic address: .
Jarrett MJ; University of Colorado School of Medicine, Department of Surgery, Division of Cardiothoracic Surgery, Aurora, Colorado.
Li A; University of Colorado School of Medicine, Department of Surgery, Division of Cardiothoracic Surgery, Aurora, Colorado.
White AM; University of Colorado School of Medicine, Department of Surgery, Division of Cardiothoracic Surgery, Aurora, Colorado.
Meng X; University of Colorado School of Medicine, Department of Surgery, Division of Cardiothoracic Surgery, Aurora, Colorado.
Fullerton DA; University of Colorado School of Medicine, Department of Surgery, Division of Cardiothoracic Surgery, Aurora, Colorado.
Weyant MJ; University of Colorado School of Medicine, Department of Surgery, Division of Cardiothoracic Surgery, Aurora, Colorado.
-
Źródło:
-
The Journal of surgical research [J Surg Res] 2021 Mar; Vol. 259, pp. 562-568. Date of Electronic Publication: 2020 Nov 28.
-
Typ publikacji:
-
Journal Article; Research Support, Non-U.S. Gov't
-
Język:
-
English
-
Imprint Name(s):
-
Publication: New York, NY : Academic Press
Original Publication: Philadelphia [etc.]
-
MeSH Terms:
-
Barrett Esophagus/*pathology
Esophagus/*pathology
Group II Phospholipases A2/*antagonists & inhibitors
Pentanoic Acids/*pharmacology
Adenocarcinoma/pathology ; Adenocarcinoma/prevention & control ; Barrett Esophagus/drug therapy ; Cell Adhesion/drug effects ; Cell Line ; Cell Proliferation/drug effects ; Drug Evaluation, Preclinical ; Esophageal Neoplasms/pathology ; Esophageal Neoplasms/prevention & control ; Esophagus/cytology ; Group II Phospholipases A2/metabolism ; Humans ; Pentanoic Acids/therapeutic use
-
Contributed Indexing:
-
Keywords: Barrett's esophagus; Intercellular adhesion molecule-1; Proliferation; Secretory phospholipase A(2); Vascular cell adhesion molecule-1
-
Substance Nomenclature:
-
0 (5-(4-benzyloxyphenyl)-4S-(7-phenylheptanoylamino)pentanoic acid)
0 (Pentanoic Acids)
EC 3.1.1.4 (Group II Phospholipases A2)
-
SCR Disease Name:
-
Adenocarcinoma Of Esophagus
-
Entry Date(s):
-
Date Created: 20201202 Date Completed: 20210504 Latest Revision: 20210504
-
Update Code:
-
20240105
-
DOI:
-
10.1016/j.jss.2020.10.018
-
PMID:
-
33261858
-
Background: Gastroesophageal reflux and Barrett's esophagus are significant risk factors for the development of esophageal adenocarcinoma. Group IIa secretory phospholipase A 2 (sPLA 2 ) catalyzes the production of various proinflammatory metabolites and plays a critical role in promoting reflux-induced inflammatory changes within the distal esophagus. We hypothesized that inhibition of sPLA 2 in human Barrett's cells would attenuate adhesion molecule expression via decreased activation of nuclear factor kappa B (NF-κB) and decrease cell proliferation, possibly mitigating the invasive potential of Barrett's esophagus.
Materials and Methods: Normal human esophageal epithelial cells (HET1A) and Barrett's cells (CPB) were assayed for baseline sPLA 2 expression. CPB cells were treated with a specific inhibitor of sPLA 2 followed by tumor necrosis factor-α. Protein expression was evaluated using immunoblotting. Cell proliferation was assessed using an MTS cell proliferation assay kit. Statistical analysis was performed using the Student's t-test or analysis of variance, where appropriate.
Results: CPB cells demonstrated higher baseline sPLA 2 expression than HET1A cells (P = 0.0005). Treatment with 30 μM sPLA 2 inhibitor significantly attenuated intercellular adhesion molecule-1 (P = 0.004) and vascular cell adhesion molecule-1 (P < 0.0001) expression as well as decreased NF-κB activation (P = 0.002). sPLA 2 inhibition decreased cell proliferation in a dose-dependent manner (P < 0.001 for 15, 20, and 30 μM doses).
Conclusions: sPLA 2 inhibition in human Barrett's cells decreases cellular adhesive properties and NF-κB activation as well as decreases cell proliferation, signifying downregulation of the inflammatory response and possible attenuation of cellular malignant potential. These findings identify sPLA 2 inhibition as a potential chemopreventive target for premalignant lesions of the esophagus.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
