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Celecoxib Prevents Doxorubicin-Induced Multidrug Resistance in Canine and Mouse Lymphoma Cell Lines
Edina Karai1,2, Kornélia Szebényi1,3, Tímea Windt1
1Institute of Enzymology, Research Centre of Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok körútja 2, H-1117 Budapest, Hungary.
Background:
Treatment of malignancies is still a major challenge in human and canine cancer, mostly due to the emergence of multidrug resistance (MDR). One of the main contributors of MDR is the overexpression P-glycoprotein (Pgp), which recognizes and extrudes various chemotherapeutics from cancer cells.
Methods:
To study mechanisms underlying the development of drug resistance, we established an in vitro treatment protocol to rapidly induce Pgp-mediated MDR in cancer cells. Based on a clinical observation showing that a 33-day-long, unplanned drug holiday can reverse the MDR phenotype of a canine diffuse large B-cell lymphoma patient, our aim was to use the established assay to prevent the emergence of drug resistance in the early stages of treatment.
Results:
We showed that an in vitro drug holiday results in the decrease of Pgp expression in MDR cell lines. Surprisingly, celecoxib, a known COX-2 inhibitor, prevented the emergence of drug-induced MDR in murine and canine lymphoma cell lines.
Conclusions:
Our findings suggest that celecoxib could significantly improve the efficiency of chemotherapy by preventing the development of MDR in B-cell lymphoma.
Insights
A drug holiday can decrease multidrug resistance (MDR) in cancer cells. Celecoxib, a COX-2 inhibitor, also prevents MDR development, potentially improving chemotherapy for lymphoma patients.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Multidrug resistance (MDR) is a significant obstacle in treating human and canine malignancies.
- Overexpression of P-glycoprotein (Pgp) is a primary driver of MDR, mediating the extrusion of chemotherapeutics from cancer cells.
Purpose of the Study:
- To investigate mechanisms underlying drug resistance development.
- To establish an in vitro model for inducing Pgp-mediated MDR.
- To explore strategies for preventing MDR emergence, inspired by a canine lymphoma case.
Main Methods:
- Developed an in vitro treatment protocol to induce Pgp-mediated MDR in cancer cells.
- Utilized a drug holiday approach based on clinical observations.
- Tested celecoxib, a COX-2 inhibitor, for its potential to prevent MDR.
Main Results:
- An in vitro drug holiday led to reduced Pgp expression in MDR cell lines.
- Celecoxib demonstrated efficacy in preventing the emergence of drug-induced MDR in murine and canine lymphoma cell lines.
Conclusions:
- Celecoxib shows potential in preventing the development of MDR in B-cell lymphoma.
- This finding suggests celecoxib could enhance chemotherapy effectiveness by mitigating MDR.
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