Cold plasma-treated medium preferentially eliminates doxorubicin-resistant osteosarcoma cells
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...
| Autores: | , , , , , , , |
|---|---|
| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/414262 |
| Acesso em linha: | http://hdl.handle.net/10261/414262 |
| Access Level: | acceso abierto |
| Palavra-chave: | Osteosarcoma Cold atmospheric plasma Oxidative stress Doxorubicin Drug-resistance |
| Resumo: | 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 DX-resistant 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. |
|---|