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

• Published in: BMC veterinary research 2013-06, Vol.9 (1), p.119-119, Article 119
• Main Authors: Pawłowski, Karol M, Mucha, Joanna, Majchrzak, Kinga, Motyl, Tomasz, Król, Magdalena
• Format: Article
• Language: English
• Subjects: Animals; Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; ATP Binding Cassette Transporter, Sub-Family B - genetics; ATP Binding Cassette Transporter, Sub-Family B - physiology; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - physiology; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - physiology; Breast cancer; Cancer; Cancer therapies; Care and treatment; Cell Line, Tumor; Dog Diseases - drug therapy; Dog Diseases - genetics; Dogs; Dosage and administration; Drug resistance; Drug Resistance, Multiple - genetics; Drug Resistance, Neoplasm - genetics; Drug therapy; Female; Flow Cytometry - veterinary; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Genetic aspects; Mammary Neoplasms, Animal - drug therapy; Mammary Neoplasms, Animal - genetics; Medical equipment and supplies industry; Medical test kit industry; Metastasis; Mortality; Oncology, Experimental; Physiological aspects; Proteins; Reverse Transcriptase Polymerase Chain Reaction - veterinary; RNA, Small Interfering - genetics; Studies; Transfection - veterinary; Tumors
• ISSN: 1746-6148; 1746-6148
• DOI: 10.1186/1746-6148-9-119

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