Repurposing Na+/K+ pump blockers for in vitro suppression of tumor development
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1
Victor Babes University of Medicine and Pharmacy Timisoara, Functional Sciences, Romania
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2
Clinical Emergency County Hospital Timisoara, Romania
It has become clear that progression of carcinomas depend not only on alterations on epithelial cells, but also on changes of microenvironment. Solid tumors survival and development is often based on vascular network sustaining such an intense metabolic process. Main purpose of our study was investigation of effects of Na/K pump blockers on tumor cells and tumor associated fibroblasts (TAF).
TAFs and breast tumor cell line SK-BR3 were used. Ouabain, Na+/K+-ATPase inhibitor, was added in cell culture media for 24 and 48 hours in concentrations ranging from 10 µM to 1 nM, and amount of cellular utilization was determined by HPLC. MTT-based viability assay showed decreased proliferation rates for higher concentration of Ouabain. Flowcytometric analysis investigated expression of phenotypical markers, including CD106, CD90, CD44, CD29, CD117, CXCR4 for TAFs, and Her2, CD44, VEGF-R and CD29 for SK-BR3 cells. Gene expression of α1 and β1 subunits of Na+/K+ pump, as well as VEGF were determined using qRT-PCR method. The results showed that VEGF secretion was significantly reduced in Ouabain-treated SK-BR3 and TAFs. Although level of expression for α1 catalytic subunit was increased in SK-BR3, we could not find presence of corresponding protein, reflected also in high levels of Ouabain detected in cellular supernatant. Expression of adhesion molecules was decreased, and we found profound changes in phenotypic profile of both TAFs and SK-BR3 cells. Based on their anti-angiogenic and
anti-proliferative activity, Na+/K+ pump inhibitors could open novel anti-tumoral therapeutic strategies.
Acknowledgements
PN II IDEI 318/2011
Keywords:
pump inhibitor,
Na/K pump,
Ouabain,
TAFs,
tumor cells
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Lazarovicz
R,
Toma
M,
Gavriliuc
O,
Marusciac
L,
Gruia
A,
Țațu
C,
Tanasie
G,
Panaitescu
C,
Bojin
FM and
Paunescu
V
(2013). Repurposing Na+/K+ pump blockers for in vitro suppression of tumor development.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00498
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Received:
15 Apr 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Mr. Radu-Adrian Lazarovicz, Victor Babes University of Medicine and Pharmacy Timisoara, Functional Sciences, Timisoara, 300041, Romania, l.radu.adrian@gmail.com