Inhibition of cell migration by ouabain in the A549 human lung cancer cell line

Liu,Ning; Li,Yali; Su,Suwen; Wang,Na; Wang,Huici; Li,Junxia

doi:10.3892/ol.2013.1406

Inhibition of cell migration by ouabain in the A549 human lung cancer cell line

Authors:
- Ning Liu
- Yali Li
- Suwen Su
- Na Wang
- Huici Wang
- Junxia Li
View Affiliations

Affiliations: The Key Laboratory of Pharmacology and Toxicology for New Drugs, Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Hebei Provincial People's Hospital, Shijiazhuang, Hebei 050051, P.R. China, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
Published online on: June 17, 2013 https://doi.org/10.3892/ol.2013.1406
Pages: 475-479

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The Na+/K+-ATPase α subunit is highly expressed in malignant cells. Ouabain, a cardioactive glycoside, binds to the Na+/K+‑ATPase α subunit and inhibits the activity of Na+/K+‑ATPase. In the present study, the effect of ouabain on the migration of A549 cells was analyzed using the wound healing and transwell chamber migration assays. The impact of ouabain on the expression of E‑cadherin, N‑cadherin, vimentin, matrix metalloprotease (MMP)‑2 and MMP‑9 was also evaluated. Ouabain treatment not only inhibited the epidermal growth factor (EGF)‑enhanced migration of A549 cells, but also inhibited the basal migration of A549 cells in the absence of EGF. Ouabain decreased the overexpression of N‑cadherin and vimentin induced by EGF, and decreased the expression of MMP‑2 and ‑9 in the presence or absence of EGF. Na+/K+‑ATPase is a potent therapeutic target in lung cancer and these observations indicated that the Na+/K+‑ATPase inhibitor, ouabain, retards the invasion of lung cancer cells.

View Figures

View References

1.	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar
2.	Greenlee RT, Murray T, Bolden S and Wingo PA: Cancer statistics, 2000. CA Cancer J Clin. 50:7–33. 2000. View Article : Google Scholar
3.	Yin W, Cheng W, Shen W, et al: Impairment of Na(+),K(+)-ATPase in CD95(APO-1)-induced human T-cell leukemia cell apoptosis mediated by glutathione depletion and generation of hydrogen peroxide. Leukemia. 21:1669–1678. 2007.
4.	Einbond LS, Shimizu M, Ma H, et al: Actein inhibits the Na⁺-K⁺-ATPase and enhances the growth inhibitory effect of digitoxin on human breast cancer cells. Biochem Biophys Res Commun. 375:608–613. 2008.PubMed/NCBI
5.	Prassas I and Diamandis EP: Novel therapeutic applications of cardiac glycosides. Nat Rev Drug Discov. 7:926–935. 2008. View Article : Google Scholar : PubMed/NCBI
6.	Haux J: Digitoxin is a potential anticancer agent for several types of cancer. Med Hypotheses. 53:543–548. 1999. View Article : Google Scholar : PubMed/NCBI
7.	Xu ZW, Wang FM, Gao MJ, et al: Cardiotonic steroids attenuate ERK phosphorylation and generate cell cycle arrest to block human hepatoma cell growth. J Steroid Biochem Mol Biol. 125:181–191. 2011. View Article : Google Scholar : PubMed/NCBI
8.	Klymkowsky MW and Savagner P: Epithelial-mesenchymal transition: a cancer researcher’s conceptual friend and foe. Am J Pathol. 174:1588–1593. 2009.PubMed/NCBI
9.	Peng CW, Liu XL, Liu X and Li Y: Co-evolution of cancer microenvironment reveals distinctive patterns of gastric cancer invasion: laboratory evidence and clinical significance. J Transl Med. 8:1012010. View Article : Google Scholar
10.	Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI
11.	Espinosa-Neira R, Mejia-Rangel J, Cortes-Reynosa P and Salazar EP: Linoleic acid induces an EMT-like process in mammary epithelial cells MCF10A. Int J Biochem Cell Biol. 43:1782–1791. 2011. View Article : Google Scholar : PubMed/NCBI
12.	Kim MA, Lee HS, Lee HE, Kim JH, Yang HK and Kim WH: Prognostic importance of epithelial-mesenchymal transition-related protein expression in gastric carcinoma. Histopathology. 54:442–451. 2009. View Article : Google Scholar : PubMed/NCBI
13.	Joost S, Almada LL, Rohnalter V, et al: GLI1 inhibition promotes epithelial-to-mesenchymal transition in pancreatic cancer cells. Cancer Res. 72:88–99. 2012. View Article : Google Scholar : PubMed/NCBI
14.	Walker S: Updates in non-small cell lung cancer. Clin J Oncol Nurs. 12:587–596. 2008. View Article : Google Scholar : PubMed/NCBI
15.	Shintani Y, Okimura A, Sato K, et al: Epithelial to mesenchymal transition is a determinant of sensitivity to chemoradiotherapy in non-small cell lung cancer. Ann Thorac Surg. 92:1794–1804. 2011. View Article : Google Scholar : PubMed/NCBI
16.	Hardy KM, Booth BW, Hendrix MJC, Salomon DS and Strizzi L: ErbB/EGF signaling and EMT in mammary development and breast cancer. J Mammary Gland Biol Neoplasia. 15:191–199. 2010. View Article : Google Scholar : PubMed/NCBI
17.	Wu K and Bonavida B: The activated NF-kappaB-Snail-RKIP circuitry in cancer regulates both the metastatic cascade and resistance to apoptosis by cytotoxic drugs. Crit Rev Immunol. 29:241–254. 2009. View Article : Google Scholar : PubMed/NCBI
18.	Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI
19.	Mariotti A, Perotti A, Sessa C and Rüegg C: N-cadherin as a therapeutic target in cancer. Expert Opin Investig Drugs. 16:451–465. 2007. View Article : Google Scholar : PubMed/NCBI
20.	Wheelock MJ, Shintani Y, Maeda M, Fukumoto Y and Johnson KR: Cadherin switching. J Cell Sci. 121:727–735. 2008. View Article : Google Scholar : PubMed/NCBI
21.	Kokkinos MI, Wafai R, Wong MK, Newgreen DF, Thompson EW and Waltham M: Vimentin and epithelial-mesenchymal transition in human breast cancer - observations in vitro and in vivo. Cells Tissues Organs. 185:191–203. 2007. View Article : Google Scholar : PubMed/NCBI
22.	Uddin MN, Horvat D, Glaser SS, et al: Marinobufagenin inhibits proliferation and migration of cytotrophoblast and CHO cells. Placenta. 29:266–273. 2008. View Article : Google Scholar : PubMed/NCBI
23.	Huang CY, Lin CY, Tsai CW and Yin MC: Inhibition of cell proliferation, invasion and migration by ursolic acid in human lung cancer cell lines. Toxicol In Vitro. 25:1274–1280. 2011. View Article : Google Scholar : PubMed/NCBI
24.	Hua H, Li M, Luo T, Yin Y and Jiang Y: Matrix metalloproteinases in tumorigenesis: an evolving paradigm. Cell Mol Life Sci. 68:3853–3868. 2011. View Article : Google Scholar : PubMed/NCBI
25.	Lin CY, Tsai PH, Kandaswami CC, et al: Matrix metalloproteinase-9 cooperates with transcription factor Snail to induce epithelial-mesenchymal transition. Cancer Sci. 102:815–827. 2011. View Article : Google Scholar : PubMed/NCBI