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Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Cold plasma-treated medium preferentially eliminates doxorubicin-resistant osteosarcoma cells
Juan Tornín1, Borja Gallego1, Verónica Rey2
1Sarcomas 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.
Abstract:
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.
Insights
Cold Plasma Treated Medium (PTM) combats doxorubicin resistance in osteosarcoma (OS) by increasing oxidative stress and reducing MDR1 expression. This approach offers a new strategy to treat drug-resistant bone cancer.
Area of Science:
- Oncology
- Biomedical Engineering
- Cancer Research
Background:
- Osteosarcoma (OS) is an aggressive bone cancer with limited treatment options.
- Doxorubicin (DX) resistance is a major challenge in OS treatment, leading to poor patient prognosis.
- Developing strategies to overcome drug resistance is crucial for improving OS outcomes.
Purpose of the Study:
- To investigate the potential of Cold Plasma Treated Medium (PTM) in overcoming doxorubicin (DX) resistance in osteosarcoma (OS).
- To elucidate the mechanisms by which PTM affects DX-resistant OS cells.
Main Methods:
- Utilized two doxorubicin (DX)-resistant osteosarcoma (OS) cell models.
- Analyzed changes in cell proliferation, MDR1 efflux pump expression, and antioxidant enzyme levels (SOD2, GPX1) during DX resistance acquisition.
- Assessed the effects of PTM treatment on oxidative stress, cell viability, and MDR1 expression in DX-resistant OS cells.
Main Results:
- DX-resistant OS cells exhibited reduced proliferation, overexpression of MDR1, and decreased SOD2/GPX1.
- PTM treatment increased oxidative stress in resistant cells.
- PTM effectively eradicated DX-resistant OS cells and reduced MDR1 expression, sensitizing them to DX.
Conclusions:
- DX-resistant OS cells possess vulnerabilities related to oxidative stress management and MDR1 dependence.
- PTM treatment can exploit these vulnerabilities to overcome DX resistance in OS.
- PTM represents a promising therapeutic approach for managing drug resistance in osteosarcoma.
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