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Repositioning of duloxetine to target pancreatic stellate cells

Pancreatic cancer cells (PCCs) are surrounded by an abundant stroma, which is produced by pancreatic stellate cells (PSCs). PSCs promote tumor cell proliferation and invasion. The objective of the current study was to identify compounds that suppress PSC activation. Gene expression profiles of cance...

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Autores principales: Sagara, Akiko, Nakata, Kohei, Matsumoto, Sokichi, Guan, Weiyu, Shinkawa, Tomohiko, Iwamoto, Chika, Ikenaga, Naoki, Ohuchida, Kenoki, Nakamura, Masafumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387862/
https://www.ncbi.nlm.nih.gov/pubmed/34466156
http://dx.doi.org/10.3892/ol.2021.13005
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author Sagara, Akiko
Nakata, Kohei
Matsumoto, Sokichi
Guan, Weiyu
Shinkawa, Tomohiko
Iwamoto, Chika
Ikenaga, Naoki
Ohuchida, Kenoki
Nakamura, Masafumi
author_facet Sagara, Akiko
Nakata, Kohei
Matsumoto, Sokichi
Guan, Weiyu
Shinkawa, Tomohiko
Iwamoto, Chika
Ikenaga, Naoki
Ohuchida, Kenoki
Nakamura, Masafumi
author_sort Sagara, Akiko
collection PubMed
description Pancreatic cancer cells (PCCs) are surrounded by an abundant stroma, which is produced by pancreatic stellate cells (PSCs). PSCs promote tumor cell proliferation and invasion. The objective of the current study was to identify compounds that suppress PSC activation. Gene expression profiles of cancer-derived fibroblasts and normal fibroblasts were used, and the pathway analysis suggested altered pathways that were chosen for validation. It was found that the ‘neuroactive ligand-receptor interaction’ pathway from the Kyoto Encyclopedia of Genes and Genomes pathway analysis was one of the altered pathways. Several compounds related with this pathway were chosen, and changes in PSC activity were investigated using fluorescence staining of lipid droplets, reverse transcription-quantitative PCR, western blotting, and invasion and migration assays. Among these candidates, duloxetine, a serotonin-noradrenaline reuptake inhibitor, was found to suppress PSC activation and disrupt tumor-stromal interaction. Thus, duloxetine may be a potential drug for suppressing PSC activation and pancreatic cancer growth.
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spelling pubmed-83878622021-08-30 Repositioning of duloxetine to target pancreatic stellate cells Sagara, Akiko Nakata, Kohei Matsumoto, Sokichi Guan, Weiyu Shinkawa, Tomohiko Iwamoto, Chika Ikenaga, Naoki Ohuchida, Kenoki Nakamura, Masafumi Oncol Lett Articles Pancreatic cancer cells (PCCs) are surrounded by an abundant stroma, which is produced by pancreatic stellate cells (PSCs). PSCs promote tumor cell proliferation and invasion. The objective of the current study was to identify compounds that suppress PSC activation. Gene expression profiles of cancer-derived fibroblasts and normal fibroblasts were used, and the pathway analysis suggested altered pathways that were chosen for validation. It was found that the ‘neuroactive ligand-receptor interaction’ pathway from the Kyoto Encyclopedia of Genes and Genomes pathway analysis was one of the altered pathways. Several compounds related with this pathway were chosen, and changes in PSC activity were investigated using fluorescence staining of lipid droplets, reverse transcription-quantitative PCR, western blotting, and invasion and migration assays. Among these candidates, duloxetine, a serotonin-noradrenaline reuptake inhibitor, was found to suppress PSC activation and disrupt tumor-stromal interaction. Thus, duloxetine may be a potential drug for suppressing PSC activation and pancreatic cancer growth. D.A. Spandidos 2021-10 2021-08-20 /pmc/articles/PMC8387862/ /pubmed/34466156 http://dx.doi.org/10.3892/ol.2021.13005 Text en Copyright: © Sagara et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Sagara, Akiko
Nakata, Kohei
Matsumoto, Sokichi
Guan, Weiyu
Shinkawa, Tomohiko
Iwamoto, Chika
Ikenaga, Naoki
Ohuchida, Kenoki
Nakamura, Masafumi
Repositioning of duloxetine to target pancreatic stellate cells
title Repositioning of duloxetine to target pancreatic stellate cells
title_full Repositioning of duloxetine to target pancreatic stellate cells
title_fullStr Repositioning of duloxetine to target pancreatic stellate cells
title_full_unstemmed Repositioning of duloxetine to target pancreatic stellate cells
title_short Repositioning of duloxetine to target pancreatic stellate cells
title_sort repositioning of duloxetine to target pancreatic stellate cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387862/
https://www.ncbi.nlm.nih.gov/pubmed/34466156
http://dx.doi.org/10.3892/ol.2021.13005
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