Drug transporter expression profiling in chemoresistant variants of the A2780 ovarian cancer cell line

Radosław Januchowski; Piotr Zawierucha; Marcin Ruciński; Małgorzata Andrzejewska; Karolina Wojtowicz; Michał Nowicki; Maciej Zabel

doi:10.1016/j.biopha.2014.02.002

Drug transporter expression profiling in chemoresistant variants of the A2780 ovarian cancer cell line

Biomed Pharmacother. 2014 May;68(4):447-53. doi: 10.1016/j.biopha.2014.02.002. Epub 2014 Apr 18.

Authors

Radosław Januchowski¹, Piotr Zawierucha², Marcin Ruciński², Małgorzata Andrzejewska², Karolina Wojtowicz², Michał Nowicki², Maciej Zabel³

Affiliations

¹ Department of Histology and Embryology, Poznań University of Medical Sciences, Święcickiego 6St., Post code 61-781, Poznań, Poland. Electronic address: rjanuchowski@wp.pl.
² Department of Histology and Embryology, Poznań University of Medical Sciences, Święcickiego 6St., Post code 61-781, Poznań, Poland.
³ Department of Histology and Embryology, Poznań University of Medical Sciences, Święcickiego 6St., Post code 61-781, Poznań, Poland; Department of Histology and Embryology, Wroclaw Medical University, Poland Chałubińskiego 6a St., 50-368 Wrocław, Poland.

PMID: 24814220
DOI: 10.1016/j.biopha.2014.02.002

Abstract

Ovarian cancer is characterized by the higher mortality among gynecological cancers. In results of MDR development during chemotherapy cancer cells become resistant to further treatment. Microarray techniques can provide information about MDR development at gene expression level. ABC and SLC transporters are most important proteins responsible for this phenomenon. In this study changes of ABC and SLC genes expression pattern in drugs resistant sublines of the A2780 ovarian cancer cell line were demonstrated. The cytostatic resistant sublines were generated by culture of A2780 cell line with an increasing concentration of the indicated drugs. As screening methods, we used Affymetrix U219 Human Genome microarrays. Independent t-tests were used to determinate statistical significances of results. Genes that expression levels were higher than assumed threshold (upregulated above threefold and downregulated under -3 fold) were visualized using scatter plot method, selected and listed in table. Between the ABC genes increased expression of seven genes and decreased expression of three genes were observed. Expression of two genes was increased or decreased depending on the cell line. We observed significant (more than tenfold) increase in expression of four ABC genes: ABCA8, ABCB1, ABCB4 and ABCG2 and decreased expression of ABCA3 gene. We also observed changes in expression of 32 SLC genes. Between them we observe increased expression of 17 genes and decreased expression of 15 genes. Expression of four genes was increased or decreased dependent on cell line. The expression of nine SLC genes increased or decreased very significantly (more than tenfold). Five genes were significantly upregulated: SLC2A9, SLC16A3, SLC16A14, SLC38A4 and SLC39A8. Four additional genes were significantly downregulated: SLC2A14, SLC6A15, SLC8A1 and SLC27A2. Expression profiles of these genes give strong arguments for assumption of correlation between expression of ABC and SLC genes and drug resistance phenomenon. Identifying correlations between specific drug transporters and cytostatic drug resistance will require further investigation.

Keywords: CDNA microarray; Drug transporters; Multidrug resistance; Ovarian cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP-Binding Cassette Transporters / genetics*
Antineoplastic Agents / pharmacology*
Biological Transport
Cell Line, Tumor
Down-Regulation
Drug Resistance, Neoplasm
Female
Gene Expression Regulation, Neoplastic
Humans
Membrane Transport Proteins / genetics*
Oligonucleotide Array Sequence Analysis
Ovarian Neoplasms / drug therapy
Ovarian Neoplasms / genetics*
Up-Regulation

Substances

ATP-Binding Cassette Transporters
Antineoplastic Agents
Membrane Transport Proteins