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Inhibition of STAT3 in gastric cancer: role of pantoprazole as SHP-1 inducer

BACKGROUND: We investigated the inhibitory effect of pantoprazole on signal transducer and activator of transcription 3 (STAT3) activity and invasiveness of gastric adenocarcinoma cells, and the role of SH2-containing protein tyrosine phosphatase 1 (SHP-1) in mediating role. METHODS: We used AGS and...

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Autores principales: Koh, Jin Sung, Joo, Moon Kyung, Park, Jong-Jae, Yoo, Hyo Soon, Choi, Byung Il, Lee, Beom Jae, Chun, Hoon Jai, Lee, Sang Woo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127946/
https://www.ncbi.nlm.nih.gov/pubmed/30202514
http://dx.doi.org/10.1186/s13578-018-0248-9
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author Koh, Jin Sung
Joo, Moon Kyung
Park, Jong-Jae
Yoo, Hyo Soon
Choi, Byung Il
Lee, Beom Jae
Chun, Hoon Jai
Lee, Sang Woo
author_facet Koh, Jin Sung
Joo, Moon Kyung
Park, Jong-Jae
Yoo, Hyo Soon
Choi, Byung Il
Lee, Beom Jae
Chun, Hoon Jai
Lee, Sang Woo
author_sort Koh, Jin Sung
collection PubMed
description BACKGROUND: We investigated the inhibitory effect of pantoprazole on signal transducer and activator of transcription 3 (STAT3) activity and invasiveness of gastric adenocarcinoma cells, and the role of SH2-containing protein tyrosine phosphatase 1 (SHP-1) in mediating role. METHODS: We used AGS and MKN-28 cells because of reduced SHP-1 and preserved p-STAT3 expression. Western blot, wound closure assay, Matrigel invasion assay and 3-D culture invasion assay were performed. Pharmacologic inhibitor of SHP-1 and siRNA were used for validation of the role of SHP-1. RESULTS: We observed that pantoprazole at 40, 80, and 160 μg/ml upregulated SHP-1 and downregulated p-STAT3 expression in a dose-dependent manner in AGS and MKN-28 cells. Furthermore, pantoprazole significantly downregulated mesenchymal markers (Snail1 and vimentin), upregulated epithelial marker (E-cadherin), and inhibited migration and invasion of AGS and MKN-28 cells. To validate the role of SHP-1 in inhibition of STAT3 activity by pantoprazole in gastric cancer cells, we performed pharmacologic inhibition (pervanadate) or knockdown of SHP-1 before pantoprazole treatment, which significantly attenuated the suppression of p-STAT3 and anti-migration and invasion effect by pantoprazole in AGS cells. In xenograft tumor model, tumor volume was significantly reduced by intraperitoneal injection of pantoprazole, with upregulation of SHP-1 and downregulation of p-STAT3, which were attenuated by concomitant injection of pervanadate. CONCLUSION: Our data suggest that the inhibitory effect of pantoprazole on cellular migration and invasion might be through inducing SHP-1 in gastric cancer cells.
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spelling pubmed-61279462018-09-10 Inhibition of STAT3 in gastric cancer: role of pantoprazole as SHP-1 inducer Koh, Jin Sung Joo, Moon Kyung Park, Jong-Jae Yoo, Hyo Soon Choi, Byung Il Lee, Beom Jae Chun, Hoon Jai Lee, Sang Woo Cell Biosci Research BACKGROUND: We investigated the inhibitory effect of pantoprazole on signal transducer and activator of transcription 3 (STAT3) activity and invasiveness of gastric adenocarcinoma cells, and the role of SH2-containing protein tyrosine phosphatase 1 (SHP-1) in mediating role. METHODS: We used AGS and MKN-28 cells because of reduced SHP-1 and preserved p-STAT3 expression. Western blot, wound closure assay, Matrigel invasion assay and 3-D culture invasion assay were performed. Pharmacologic inhibitor of SHP-1 and siRNA were used for validation of the role of SHP-1. RESULTS: We observed that pantoprazole at 40, 80, and 160 μg/ml upregulated SHP-1 and downregulated p-STAT3 expression in a dose-dependent manner in AGS and MKN-28 cells. Furthermore, pantoprazole significantly downregulated mesenchymal markers (Snail1 and vimentin), upregulated epithelial marker (E-cadherin), and inhibited migration and invasion of AGS and MKN-28 cells. To validate the role of SHP-1 in inhibition of STAT3 activity by pantoprazole in gastric cancer cells, we performed pharmacologic inhibition (pervanadate) or knockdown of SHP-1 before pantoprazole treatment, which significantly attenuated the suppression of p-STAT3 and anti-migration and invasion effect by pantoprazole in AGS cells. In xenograft tumor model, tumor volume was significantly reduced by intraperitoneal injection of pantoprazole, with upregulation of SHP-1 and downregulation of p-STAT3, which were attenuated by concomitant injection of pervanadate. CONCLUSION: Our data suggest that the inhibitory effect of pantoprazole on cellular migration and invasion might be through inducing SHP-1 in gastric cancer cells. BioMed Central 2018-09-06 /pmc/articles/PMC6127946/ /pubmed/30202514 http://dx.doi.org/10.1186/s13578-018-0248-9 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Koh, Jin Sung
Joo, Moon Kyung
Park, Jong-Jae
Yoo, Hyo Soon
Choi, Byung Il
Lee, Beom Jae
Chun, Hoon Jai
Lee, Sang Woo
Inhibition of STAT3 in gastric cancer: role of pantoprazole as SHP-1 inducer
title Inhibition of STAT3 in gastric cancer: role of pantoprazole as SHP-1 inducer
title_full Inhibition of STAT3 in gastric cancer: role of pantoprazole as SHP-1 inducer
title_fullStr Inhibition of STAT3 in gastric cancer: role of pantoprazole as SHP-1 inducer
title_full_unstemmed Inhibition of STAT3 in gastric cancer: role of pantoprazole as SHP-1 inducer
title_short Inhibition of STAT3 in gastric cancer: role of pantoprazole as SHP-1 inducer
title_sort inhibition of stat3 in gastric cancer: role of pantoprazole as shp-1 inducer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127946/
https://www.ncbi.nlm.nih.gov/pubmed/30202514
http://dx.doi.org/10.1186/s13578-018-0248-9
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