Ouabain Suppresses Cell Migration and Invasion in Human Gastric Cancer AGS Cells Through the Inhibition of MMP Signaling Pathways.

Abstract

BACKGROUND/AIM:

Ouabain has been shown to induce human cancer cell death via apoptosis. Still, its anti-metastatic effect on cell migration and invasion of human gastric cancer cells has not been addressed.

MATERIALS AND METHODS:

Cell proliferation and viability were measured by the MTT assay and flow cytometry, respectively. Cell motitlity was analysed by wound healing assay. Cell migration and invasion were analysed by the transwell system. Protein expression was assayed by western blotting.

RESULTS:

Ouabain decreased AGS cell proliferation, cell viability, and motility. In addition, ouabain inhibited AGS cell migration and invasion. Furthermore, ouabain decreased matrix metalloproteinase-2 (MMP-2) activity at 48 h. Ouabain reduced the levels of proteins associated with PI3K/AKT and p38/MAPK pathways. In addition, ouabain decreased the expressions of N-cadherin, tissue inhibitor of metalloproteinases-1 (TIMP-1), urokinase-type plasminogen activator (c-uPA), and MMP-2 at 48 h.

CONCLUSION:

Ouabain suppresses cell metastasis through multiple signaling pathways in AGS cells.

• Authors: Hung-Yi Chen, Mei-Due Yang, Yu-Cheng Chou, Yi-Shih Ma, Shu-Fen Peng, Ching-Lung Liao, Po-Yuan Chen, Te-Chun Hsia, Jin-Cherng Lien, Chung-Hung Chen
• Journal: Anticancer research (Anticancer Res) Vol. 41 Issue 9 Pg. 4365-4375 (Sep 2021) ISSN: 1791-7530 [Electronic] Greece
• PMID: 34475056 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Antigens, CD
• CDH2 protein, human
• Cadherins
• TIMP1 protein, human
• Tissue Inhibitor of Metalloproteinase-1
• Ouabain
• MMP2 protein, human
• Matrix Metalloproteinase 2

Topics

• Antigens, CD (metabolism)
• Cadherins (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• MAP Kinase Signaling System (drug effects)
• Matrix Metalloproteinase 2 (metabolism)
• Neoplasm Invasiveness
• Ouabain (pharmacology)
• Signal Transduction (drug effects)
• Stomach Neoplasms (drug therapy, metabolism)
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)