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Open Access 01-12-2016 | Research

Analysis of MDR genes expression and cross-resistance in eight drug resistant ovarian cancer cell lines

Authors: Radosław Januchowski, Karolina Sterzyńska, Katarzyna Zaorska, Patrycja Sosińska, Andrzej Klejewski, Maciej Brązert, Michał Nowicki, Maciej Zabel

Published in: Journal of Ovarian Research | Issue 1/2016

Abstract

Background

Multiple drug resistance (MDR) of cancer cells is the main reason of intrinsic or acquired insensitivity to chemotherapy in many cancers. In this study we used ovarian cancer model of acquired drug resistance to study development of MDR.

We have developed eight drug resistant cell lines from A2780 ovarian cancer cell line: two cell lines resistant to each drug commonly used in ovarian cancer chemotherapy: cisplatin (CIS), paclitaxel (PAC), doxorubicin (DOX) and topotecan (TOP). A chemosensitivity assay - MTT was performed to assess drug cross-resistance. Quantitative real-time polymerase chain reaction and immunofluorescence were also performed to determine mRNA and protein expression of genes/proteins involved in drug resistance (P-gp, BCRP, MRP1, MRP2, MVP). Flow cytometry was used to determine the activity of drug transporters.

Results

We could observe cross-resistance between PAC- and DOX-resistant cell lines. Additionally, both PAC-resistant cell lines were cross-resistant to TOP and both TOP-resistant cell lines were cross-resistant to DOX. We observed two different mechanisms of resistance to TOP related to P-gp and BCRP expression and activity. P-gp and BCRP were also involved in DOX resistance. Expression of MRP2 was increased in CIS-resistant cell lines and increased MVP expression was observed in CIS-, PAC- and TOP-, but not in DOX-resistant cell lines.

Conclusions

Effectiveness of TOP and DOX in second line of chemotherapy in ovarian cancer can be limited because of their cross-resistance to PAC. Moreover, cross-resistance of PAC-resistant cell line to CIS suggests that such interaction between those drugs might also be probable in clinic.

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Title: Analysis of MDR genes expression and cross-resistance in eight drug resistant ovarian cancer cell lines
Authors: Radosław Januchowski
Karolina Sterzyńska
Katarzyna Zaorska
Patrycja Sosińska
Andrzej Klejewski
Maciej Brązert
Michał Nowicki
Maciej Zabel
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Journal of Ovarian Research / Issue 1/2016
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/s13048-016-0278-z

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Analysis of MDR genes expression and cross-resistance in eight drug resistant ovarian cancer cell lines

Abstract

Background

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Results

Conclusions

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