Canine mammary carcinoma cell line are resistant to chemosensitizers: verapamil and cyclosporin A

Król, Magdalena; Pawłowski, Krzysztof; Majchrzak, Kinga; Mucha, Joanna; Motyl, T.

doi:10.2478/pjvs-2014-0002

Cited by 9 publications

(5 citation statements)

References 17 publications

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“…Drug resistance to vinblastine in CMTs cell lines is documented [30] and a high expression of P-gp [29] and BCRP [28] in CMT cell lines led to the conclusion that the use of DOX could lead to chemoresistance in treated bitches [28].…”

Section: P-gp and Bcrp Changes At Gene Expression And Cellular Phenotype Levels After Exposure To Doxorubicinmentioning

confidence: 99%

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Doxorubicin treatment modulates chemoresistance and affects the cell cycle in two canine mammary tumour cell lines

et al. 2021

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Background Doxorubicin (DOX) is widely used in both human and veterinary oncology although the onset of multidrug resistance (MDR) in neoplastic cells often leads to chemotherapy failure. Better understanding of the cellular mechanisms that circumvent chemotherapy efficacy is paramount. The aim of this study was to investigate the response of two canine mammary tumour cell lines, CIPp from a primary tumour and CIPm, from its lymph node metastasis, to exposure to EC50(20h) DOX at 12, 24 and 48 h of treatment. We assessed the uptake and subcellular distribution of DOX, the expression and function of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP), two important MDR mediators. To better understand this phenomenon the effects of DOX on the cell cycle and Ki67 cell proliferation index and the expression of p53 and telomerase reverse transcriptase (TERT) were also evaluated by immunocytochemistry (ICC). Results Both cell lines were able to uptake DOX within the nucleus at 3 h treatment while at 48 h DOX was absent from the intracellular compartment (assessed by fluorescence microscope) in all the surviving cells. CIPm, originated from the metastatic tumour, were more efficient in extruding P-gp substrates. By ICC and qRT-PCR an overall increase in both P-gp and BCRP were observed at 48 h of EC50(20h) DOX treatment in both cell lines and were associated with a striking increase in the percentage of p53 and TERT expressing cells by ICC. The cell proliferation fraction was decreased at 48 h in both cell lines and cell cycle analysis showed a DOX-induced arrest in the S phase for CIPp, while CIPm had an increase in cellular death without arrest. Both cells lines were therefore composed by a fraction of cells sensible to DOX that underwent apoptosis/necrosis. Conclusions DOX administration results in interlinked modifications in the cellular population including a substantial effect on the cell cycle, in particular arrest in the S phase for CIPp and the selection of a subpopulation of neoplastic cells bearing MDR phenotype characterized by P-gp and BCRP expression, TERT activation, p53 accumulation and decrease in the proliferating fraction. Important information is given for understanding the dynamic and mechanisms of the onset of drug resistance in a neoplastic cell population.

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Section: P-gp and Bcrp Changes At Gene Expression And Cellular Phenotype Levels After Exposure To Doxorubicinmentioning

confidence: 99%

“…P-gp and BCRP expression in CMTs has been demonstrated using techniques able to detect their presence at the subcellular level [22][23][24][25][26][27], however studies investigating the functionality of the pumps with regard to the chemotherapeutic exposure are still incipient in the dog [28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin treatment modulates chemoresistance and affects the cell cycle in two canine mammary tumour cell lines

et al. 2021

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“…Król et al (2014) treated with vinblastine two canine mammary tumors cell lines (CMT-W1 and CMT-W2) and two cell lines isolated from their lung metastases (CMT-W1M and CMT-W2M) in order to evaluate the effect of P-gp inhibitors verapamil and cyclosporine A and their possible implication in multidrug resistance. The results from qRT-PCR revealed that the multidrug-resistance gene (MDR1) known to be involved in P-gp synthesis was overexpressed in all canine mammary cell lines [ 141 ].…”

Section: Introductionmentioning

confidence: 99%

In vitro comparative models for canine and human breast cancers

Vișan¹,

Bălăcescu

Berindan‐Neagoe

et al. 2016

Medicine and Pharmacy Reports

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During the past four decades, an increased number of similarities between canine mammary tumors and human breast cancer have been reported: molecular, histological, morphological, clinical and epidemiological, which lead to comparative oncological studies. One of the most important goals in human and veterinary oncology is to discover potential molecular biomarkers that could detect breast cancer in an early stage and to develop new effective therapies. Recently, cancer cell lines have successfully been used as an in vitro model to study the biology of cancer, to investigate molecular pathways and to test the efficiency of anticancer drugs. Moreover, establishment of an experimental animal model for the study of human breast cancer will improve testing potential anti-cancer therapies and the discovery of effective therapeutic schemes suitable for human clinical trials.In this review, we collected data from previous studies that strengthen the value of canine mammary cancer cell lines as an in vitro model for the study of human breast cancer.

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“…Chemotherapeutic molecules like anthracycline are substrates of many ABC transporters, and the onset of chemoresistance to these compounds has been attributed to the expression of P-gp and BCRP in human oncology. 14,45,47 Some studies on canine mammary tumors have investigated P-gp and BCRP expression, 4,16,25,28,32,33,49,53 but the role of these chemoresistance modulators is still incipient. A previous study designed and carried out by some of the present study’s authors (M.L., B.B., G.S., C.B.)…”

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confidence: 99%

P-Glycoprotein and Breast Cancer Resistance Protein in Canine Inflammatory and Noninflammatory Grade III Mammary Carcinomas

et al. 2019

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P-glycoprotein (P-gp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) expression are frequently related to multidrug resistance (MDR) in neoplastic cells. Canine inflammatory and grade III noninflammatory mammary carcinomas (IMC and non-IMC) are aggressive tumors that could benefit from chemotherapy. This study describes the immunohistochemical detection of P-gp and BCRP in 20 IMCs and 18 non-IMCs from dogs that had not received chemotherapy. Our aim was to determine if P-gp and BCRP expression was related to the “inflammatory” phenotype, to establish a basis for future studies analyzing the response to chemotherapy in dogs with highly malignant mammary cancer. Immunolabeling was primarily membranous for P-gp with a more intense labeling in emboli, and immunolabeling was membranous and cytoplasmic for BCRP. P-gp was expressed in 17 of 20 (85%) IMCs compared to 7 of 18 (39%) non-IMCs ( P = 0.006). BCRP was expressed within emboli in 15 of 19 (79%) emboli in IMC, 12 of 15 (80%) primary IMCs, and 12 of 18 (67%) non-IMCs, without statistically significant differences ( P > .05). All IMCs and 67% of non-IMCs expressed at least 1 of the 2 transporters, and 63% (12/19) of IMCs and 39% (7/18) of non-IMCs expressed both P-gp and BCRP. P-gp and BCRP evaluation might help select patients for chemotherapy. P-gp, expressed in a significantly higher percentage of IMCs vs non-IMCs, might play a specific role in the chemoresistance of IMC.

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Canine mammary carcinoma cell line are resistant to chemosensitizers: verapamil and cyclosporin A

Cited by 9 publications

References 17 publications

Doxorubicin treatment modulates chemoresistance and affects the cell cycle in two canine mammary tumour cell lines

Doxorubicin treatment modulates chemoresistance and affects the cell cycle in two canine mammary tumour cell lines

In vitro comparative models for canine and human breast cancers

P-Glycoprotein and Breast Cancer Resistance Protein in Canine Inflammatory and Noninflammatory Grade III Mammary Carcinomas

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