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, Beom Jae Lee, Hoon Jai Chun, Sang Woo Lee

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9 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

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)

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    Koh, J. S., Joo, M. K., Park, J. J., Yoo, H. S., Choi, B. I., Lee, B. J., Chun, H. J., & Lee, S. W. (2018). Inhibition of STAT3 in gastric cancer: Role of pantoprazole as SHP-1 inducer. Cell and Bioscience, 8(1), [50]. https://doi.org/10.1186/s13578-018-0248-9