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

Jin Sung Koh, Moon Kyung Joo, Jong Jae Park, Hyo Soon Yoo, Byung Il Choi, Beomjae Lee, Hoon-Jai Chun, Sang Woo Lee

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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 160μg/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.

Original languageEnglish
Article number50
JournalCell and Bioscience
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Sep 6

Fingerprint

Protein Phosphatase 1
STAT3 Transcription Factor
Protein Tyrosine Phosphatases
Stomach Neoplasms
Assays
Down-Regulation
Tumors
Cells
pantoprazole
Vimentin
Cadherins
Tumor Burden
Intraperitoneal Injections
Heterografts
Small Interfering RNA
Stomach
Adenocarcinoma
Up-Regulation
Western Blotting
Injections

Keywords

  • Gastric cancer
  • Pantoprazole
  • SH2-containing protein tyrosine phosphatase 1
  • Signal transducer and activator of transcription 3

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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, Beomjae; Chun, Hoon-Jai; Lee, Sang Woo.

In: Cell and Bioscience, Vol. 8, No. 1, 50, 06.09.2018.

Research output: Contribution to journalArticle

@article{91a9ddcff0fd41e5a1a7fbeed7e8099f,
title = "Inhibition of STAT3 in gastric cancer: Role of pantoprazole as SHP-1 inducer",
abstract = "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 160μg/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.",
keywords = "Gastric cancer, Pantoprazole, SH2-containing protein tyrosine phosphatase 1, Signal transducer and activator of transcription 3",
author = "Koh, {Jin Sung} and Joo, {Moon Kyung} and Park, {Jong Jae} and Yoo, {Hyo Soon} and Choi, {Byung Il} and Beomjae Lee and Hoon-Jai Chun and Lee, {Sang Woo}",
year = "2018",
month = "9",
day = "6",
doi = "10.1186/s13578-018-0248-9",
language = "English",
volume = "8",
journal = "Cell and Bioscience",
issn = "2045-3701",
publisher = "Society of Chinese Bioscientists in America",
number = "1",

}

TY - JOUR

T1 - Inhibition of STAT3 in gastric cancer

T2 - Role of pantoprazole as SHP-1 inducer

AU - Koh, Jin Sung

AU - Joo, Moon Kyung

AU - Park, Jong Jae

AU - Yoo, Hyo Soon

AU - Choi, Byung Il

AU - Lee, Beomjae

AU - Chun, Hoon-Jai

AU - Lee, Sang Woo

PY - 2018/9/6

Y1 - 2018/9/6

N2 - 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 160μg/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.

AB - 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 160μg/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.

KW - Gastric cancer

KW - Pantoprazole

KW - SH2-containing protein tyrosine phosphatase 1

KW - Signal transducer and activator of transcription 3

UR - http://www.scopus.com/inward/record.url?scp=85052954241&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052954241&partnerID=8YFLogxK

U2 - 10.1186/s13578-018-0248-9

DO - 10.1186/s13578-018-0248-9

M3 - Article

AN - SCOPUS:85052954241

VL - 8

JO - Cell and Bioscience

JF - Cell and Bioscience

SN - 2045-3701

IS - 1

M1 - 50

ER -