Arsenic trioxide attenuates STAT-3 activity and epithelial-mesenchymal transition through induction of SHP-1 in gastric cancer cells

Sung Ho Kim, Hyo Soon Yoo, Moon Kyung Joo, Taehyun Kim, Jong Jae Park, Beomjae Lee, Hoon-Jai Chun, Sang Woo Lee, Young-Tae Bak

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: We investigated the effect of arsenic trioxide (ATO) for inhibition of signal transducer and activator of transcription 3 (STAT3) and epithelial-mesenchymal transition (EMT) in gastric cancer cells, and the role of SH2 domain-containing phosphatase-1 (SHP-1) during this process. Methods: We used AGS cells, which showed minimal SHP-1 expression and constitutive STAT3 expression. After treatment of ATO, cellular migration and invasion were assessed by using wound closure assay, Matrigel invasion assay and 3-D culture invasion assay. To validate the role of SHP-1, pervanadate, a pharmacologic phosphatase inhibitor, and SHP-1 siRNA were used. Xenograft tumors were produced, and ATO or pervanadate were administered via intraperitoneal (IP) route. Results: Treatment of ATO 5 and 10 μM significantly decreased cellular migration and invasion in a dose-dependent manner. Western blot showed that ATO upregulated SHP-1 expression and downregulated STAT3 expression, and immunofluorescence showed upregulation with E-cadherin (epithelial marker) and downregulation of Snail1 (mesenchymal marker) expression by ATO treatment. Anti-migration and invasion effect and modulation of SHP-1/STAT3 axis by ATO were attenuated by pervanadate or SHP-1 siRNA. IP injection of ATO significantly decreased the xenograft tumor volume and upregulated SHP-1 expression, which were attenuated by co-IP injection of pervanadate. Conclusion: Our data suggest that ATO inhibits STAT3 activity and EMT process by upregulation of SHP-1 in gastric cancer cells.

Original languageEnglish
Article number150
JournalBMC Cancer
Volume18
Issue number1
DOIs
Publication statusPublished - 2018 Feb 6

Fingerprint

Epithelial-Mesenchymal Transition
src Homology Domains
Phosphoric Monoester Hydrolases
Stomach Neoplasms
STAT3 Transcription Factor
Intraperitoneal Injections
Heterografts
Small Interfering RNA
Up-Regulation
Down-Regulation
arsenic trioxide
Cadherins
Tumor Burden
Fluorescent Antibody Technique
Therapeutics
Western Blotting

Keywords

  • Arsenic trioxide
  • Epithelial-mesenchymal transition
  • SH2-containing protein tyrosine phosphatase 1
  • Signal transducer and activator of transcription 3

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Arsenic trioxide attenuates STAT-3 activity and epithelial-mesenchymal transition through induction of SHP-1 in gastric cancer cells. / Kim, Sung Ho; Yoo, Hyo Soon; Joo, Moon Kyung; Kim, Taehyun; Park, Jong Jae; Lee, Beomjae; Chun, Hoon-Jai; Lee, Sang Woo; Bak, Young-Tae.

In: BMC Cancer, Vol. 18, No. 1, 150, 06.02.2018.

Research output: Contribution to journalArticle

@article{fb2bbff9151441edbf1555b5845aa925,
title = "Arsenic trioxide attenuates STAT-3 activity and epithelial-mesenchymal transition through induction of SHP-1 in gastric cancer cells",
abstract = "Background: We investigated the effect of arsenic trioxide (ATO) for inhibition of signal transducer and activator of transcription 3 (STAT3) and epithelial-mesenchymal transition (EMT) in gastric cancer cells, and the role of SH2 domain-containing phosphatase-1 (SHP-1) during this process. Methods: We used AGS cells, which showed minimal SHP-1 expression and constitutive STAT3 expression. After treatment of ATO, cellular migration and invasion were assessed by using wound closure assay, Matrigel invasion assay and 3-D culture invasion assay. To validate the role of SHP-1, pervanadate, a pharmacologic phosphatase inhibitor, and SHP-1 siRNA were used. Xenograft tumors were produced, and ATO or pervanadate were administered via intraperitoneal (IP) route. Results: Treatment of ATO 5 and 10 μM significantly decreased cellular migration and invasion in a dose-dependent manner. Western blot showed that ATO upregulated SHP-1 expression and downregulated STAT3 expression, and immunofluorescence showed upregulation with E-cadherin (epithelial marker) and downregulation of Snail1 (mesenchymal marker) expression by ATO treatment. Anti-migration and invasion effect and modulation of SHP-1/STAT3 axis by ATO were attenuated by pervanadate or SHP-1 siRNA. IP injection of ATO significantly decreased the xenograft tumor volume and upregulated SHP-1 expression, which were attenuated by co-IP injection of pervanadate. Conclusion: Our data suggest that ATO inhibits STAT3 activity and EMT process by upregulation of SHP-1 in gastric cancer cells.",
keywords = "Arsenic trioxide, Epithelial-mesenchymal transition, SH2-containing protein tyrosine phosphatase 1, Signal transducer and activator of transcription 3",
author = "Kim, {Sung Ho} and Yoo, {Hyo Soon} and Joo, {Moon Kyung} and Taehyun Kim and Park, {Jong Jae} and Beomjae Lee and Hoon-Jai Chun and Lee, {Sang Woo} and Young-Tae Bak",
year = "2018",
month = "2",
day = "6",
doi = "10.1186/s12885-018-4071-9",
language = "English",
volume = "18",
journal = "BMC Cancer",
issn = "1471-2407",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Arsenic trioxide attenuates STAT-3 activity and epithelial-mesenchymal transition through induction of SHP-1 in gastric cancer cells

AU - Kim, Sung Ho

AU - Yoo, Hyo Soon

AU - Joo, Moon Kyung

AU - Kim, Taehyun

AU - Park, Jong Jae

AU - Lee, Beomjae

AU - Chun, Hoon-Jai

AU - Lee, Sang Woo

AU - Bak, Young-Tae

PY - 2018/2/6

Y1 - 2018/2/6

N2 - Background: We investigated the effect of arsenic trioxide (ATO) for inhibition of signal transducer and activator of transcription 3 (STAT3) and epithelial-mesenchymal transition (EMT) in gastric cancer cells, and the role of SH2 domain-containing phosphatase-1 (SHP-1) during this process. Methods: We used AGS cells, which showed minimal SHP-1 expression and constitutive STAT3 expression. After treatment of ATO, cellular migration and invasion were assessed by using wound closure assay, Matrigel invasion assay and 3-D culture invasion assay. To validate the role of SHP-1, pervanadate, a pharmacologic phosphatase inhibitor, and SHP-1 siRNA were used. Xenograft tumors were produced, and ATO or pervanadate were administered via intraperitoneal (IP) route. Results: Treatment of ATO 5 and 10 μM significantly decreased cellular migration and invasion in a dose-dependent manner. Western blot showed that ATO upregulated SHP-1 expression and downregulated STAT3 expression, and immunofluorescence showed upregulation with E-cadherin (epithelial marker) and downregulation of Snail1 (mesenchymal marker) expression by ATO treatment. Anti-migration and invasion effect and modulation of SHP-1/STAT3 axis by ATO were attenuated by pervanadate or SHP-1 siRNA. IP injection of ATO significantly decreased the xenograft tumor volume and upregulated SHP-1 expression, which were attenuated by co-IP injection of pervanadate. Conclusion: Our data suggest that ATO inhibits STAT3 activity and EMT process by upregulation of SHP-1 in gastric cancer cells.

AB - Background: We investigated the effect of arsenic trioxide (ATO) for inhibition of signal transducer and activator of transcription 3 (STAT3) and epithelial-mesenchymal transition (EMT) in gastric cancer cells, and the role of SH2 domain-containing phosphatase-1 (SHP-1) during this process. Methods: We used AGS cells, which showed minimal SHP-1 expression and constitutive STAT3 expression. After treatment of ATO, cellular migration and invasion were assessed by using wound closure assay, Matrigel invasion assay and 3-D culture invasion assay. To validate the role of SHP-1, pervanadate, a pharmacologic phosphatase inhibitor, and SHP-1 siRNA were used. Xenograft tumors were produced, and ATO or pervanadate were administered via intraperitoneal (IP) route. Results: Treatment of ATO 5 and 10 μM significantly decreased cellular migration and invasion in a dose-dependent manner. Western blot showed that ATO upregulated SHP-1 expression and downregulated STAT3 expression, and immunofluorescence showed upregulation with E-cadherin (epithelial marker) and downregulation of Snail1 (mesenchymal marker) expression by ATO treatment. Anti-migration and invasion effect and modulation of SHP-1/STAT3 axis by ATO were attenuated by pervanadate or SHP-1 siRNA. IP injection of ATO significantly decreased the xenograft tumor volume and upregulated SHP-1 expression, which were attenuated by co-IP injection of pervanadate. Conclusion: Our data suggest that ATO inhibits STAT3 activity and EMT process by upregulation of SHP-1 in gastric cancer cells.

KW - Arsenic trioxide

KW - Epithelial-mesenchymal transition

KW - SH2-containing protein tyrosine phosphatase 1

KW - Signal transducer and activator of transcription 3

UR - http://www.scopus.com/inward/record.url?scp=85041428505&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041428505&partnerID=8YFLogxK

U2 - 10.1186/s12885-018-4071-9

DO - 10.1186/s12885-018-4071-9

M3 - Article

C2 - 29409467

AN - SCOPUS:85041428505

VL - 18

JO - BMC Cancer

JF - BMC Cancer

SN - 1471-2407

IS - 1

M1 - 150

ER -