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BioMed Research International
Volume 2013 (2013), Article ID 241763, 10 pages
http://dx.doi.org/10.1155/2013/241763
Research Article

MDR Gene Expression Analysis of Six Drug-Resistant Ovarian Cancer Cell Lines

1Department of Histology and Embryology, Poznań University of Medical Sciences, 61-781 Poznań, Poland
2Department of Histology and Embryology, Wrocław Medical University, 50-368 Wrocław, Poland

Received 18 September 2012; Accepted 21 November 2012

Academic Editor: Antonio La Gioia

Copyright © 2013 Radosław Januchowski et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Ovarian cancer is the leading cause of death among gynaecological malignancies. Multiple drug resistance makes cancer cells insensitive to chemotherapy. In this study, we developed six primary ovarian cancer cell lines (W1MR, W1CR, W1DR, W1VR, W1TR, and W1PR) resistant to drugs such as methotrexate, cisplatin, doxorubicin, vincristine, topotecan, and paclitaxel. A chemosensitivity assay MTT test was performed to assess drug cross-resistance. Quantitative real-time polymerase chain reaction and Western blot were also performed to determine mRNA and protein expression of genes involved in chemoresistance. We observed high cross-resistance to doxorubicin, vincristine, and paclitaxel in the cell lines resistant to these agents. We also found a significant correlation between resistance to these drugs and increased expression of P-gp. Two different mechanisms of topotecan resistance were observed in the W1TR and W1PR cell lines. We did not observe any correlation between MRP2 transcript and protein levels. Cell lines resistant to agents used in ovarian cancer treatment remained sensitive to methotrexate. The main mechanisms of drug resistance were due to P-gp expression in the doxorubicin, vincristine, and paclitaxel resistant cell lines and BCRP expression in the topotecan resistant cell line.