Cold plasma-treated medium preferentially eliminates doxorubicin-resistant osteosarcoma cells
Por:
Tornín J, Gallego B, Rey V, Murillo D, Huergo C, Rodríguez A, Canal-Barnils C and Rodríguez R
Publicada:
20 nov 2023
Ahead of Print:
1 oct 2023
Resumen:
Osteosarcoma (OS) is an aggressive bone cancer with poor prognosis, largely due to the limited effectiveness of current treatments such as doxorubicin (DX). Developing ways to overcome DX resistance is a significant clinical challenge. Here, we used two DX-resistant models to study the potential of Cold Plasma Treated Medium (PTM) to prevent DX resistance in OS. During the acquisition of the resistant phenotype upon long-term DX exposure, OS resistant cells became less proliferative, overexpressed the drug resistance-related efflux pump MDR1 and displayed a concomitant loss of SOD2 or GPX1. According to the reduced expression of these antioxidant enzymes, PTM treatment produced higher levels of oxidative express and was more effective in eradicating DXresistant cells. Moreover, PTM reduced the expression of MDR1, thus sensitizing resistant cells to DX. These findings uncover new vulnerabilities of DX-resistant cells related with their inability to cope with excessive oxidative stress and their dependence on MDR1 that can be exploited using PTM-based treatments to provide new therapeutic approaches for the management of drug resistance in OS.
Filiaciones:
Tornín J:
Sarcomas and Experimental Therapeutics Laboratory, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, Avenida de Roma, s/n, 33011, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias, 33011, Oviedo, Spain
Gallego B:
Sarcomas and Experimental Therapeutics Laboratory, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, Avenida de Roma, s/n, 33011, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias, 33011, Oviedo, Spain
Rey V:
Sarcomas and Experimental Therapeutics Laboratory, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, Avenida de Roma, s/n, 33011, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias, 33011, Oviedo, Spain
CIBER en oncología (CIBERONC), 28029, Madrid, Spain
Murillo D:
Sarcomas and Experimental Therapeutics Laboratory, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, Avenida de Roma, s/n, 33011, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias, 33011, Oviedo, Spain
Huergo C:
Sarcomas and Experimental Therapeutics Laboratory, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, Avenida de Roma, s/n, 33011, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias, 33011, Oviedo, Spain
Rodríguez A:
Sarcomas and Experimental Therapeutics Laboratory, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, Avenida de Roma, s/n, 33011, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias, 33011, Oviedo, Spain
Canal-Barnils C:
Biomaterials, Biomechanics and Tissue Engineering Group, Materials Science and Engineering Department, Research Center for Biomedical Engineering, Universitat Politècnica de Catalunya·BarcelonaTECH (UPC), Escola d'Enginyeria Barcelona Est (EEBE), C/Eduard Maristany 14, 08019, Barcelona, Spain
Institut de Recerca Sant Joan de Déu, 08034, Barcelona, Spain
Barcelona Research Center in Multiscale Science and Engineering, UPC, 08019, Barcelona, Spain
Rodríguez R:
Sarcomas and Experimental Therapeutics Laboratory, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, Avenida de Roma, s/n, 33011, Oviedo, Spain
Instituto Universitario de Oncología del Principado de Asturias, 33011, Oviedo, Spain
CIBER en oncología (CIBERONC), 28029, Madrid, Spain
hybrid
|