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Open Access Highly Accessed Research article

Expression and role of PGP, BCRP, MRP1 and MRP3 in multidrug resistance of canine mammary cancer cells

Karol M Pawłowski12, Joanna Mucha1, Kinga Majchrzak3, Tomasz Motyl1 and Magdalena Król1*

Author Affiliations

1 Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - WULS, Nowoursynowska 159, 02-776, Warsaw, Poland

2 Department of Large Animal Diseases with Clinic, Faculty of Veterinary Medicine, Warsaw University of Life Sciences – WULS, Nowoursynowska 100, 02-797, Warsaw, Poland

3 Department of Animal Environment Biology, Faculty of Animal Sciences, Warsaw University of Life Sciences - WULS, Ciszewskiego 8, 02-786, Warsaw, Poland

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BMC Veterinary Research 2013, 9:119  doi:10.1186/1746-6148-9-119

Published: 17 June 2013

Abstract

Background

In both women and female dogs, the most prevalent type of malignant neoplasm is the spontaneous mammary tumor. In dogs, half of these are malignant. The treatment of choice for the canine patients is surgical mastectomy. Unfortunately, it often fails in high-risk, locally invasive mammary tumors as of during the time of the surgery the micro-metastases are present. Moreover, there are neither large studies conducting to prove of the benefit from the chemotherapy in dogs nor established chemotherapy treatment protocols available. Additionally, the effectiveness of each individual chemotherapeutic agent and drug resistance of canine mammary cancer have not yet been characterized. That has become the aim of our study, to assess the expression of PGP, BCRP, MRP1 and MRP3 in canine mammary cancer cell lines and to investigate their role in cancer resistance to vinblastine, cisplatin and cyclophosphamide with using RNAi approach.

Results

The results suggested that in canine mammary cancer, the vinblastine efflux was mediated by PGP and MRP1 proteins, cisplatin efflux was mediated by all four examined efflux pumps (PGP, BCRP, MRP1 and MRP3), whereas cyclophosphamide resistance was related to BCRP activity. RNAi silencing of these efflux pumps significantly decreased IC50 doses of the examined drugs in canine mammary carcinoma cells.

Conclusions

Our results have indicated the treatment of cells involving use of the siRNA targeting efflux pumps could be a beneficial approach in the future.

Keywords:
Multidrug resistance; Chemotherapy; Canine mammary cancer; Vinblastine; Cisplatin; Cyclophosphamide; PGP; BCRP; MRP1; MRP3