Abstract

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

Highlights

  • IntroductionThat 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

  • In both women and female dogs, the most prevalent type of malignant neoplasm is the spontaneous mammary tumor

  • In human cancer over-expression of PGP is linked to resistance to vinca alkaloids, anthracyclines, epipodophyllotoxins and tubulin polymerizing drugs whereas MRP1 is responsible for resistance to vincristine and vinblastine, methothrexate, anthracyclines, etoposide, paclitaxel and irinotecan [8,9]

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Summary

Introduction

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. In both women and female dogs, the most prevalent type of malignant neoplasm is the spontaneous mammary tumor. The treatment of choice for the canine patients is surgical mastectomy It is often recognized - The resistance to a specific cytotoxic drug is ensured by the activity of efflux pumps that belong to the ABCtransporters super family. There is just one document published showing that BCRP can fully protect canine mammary cancer cells against doxorubicin [10]

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