Abstract
Osteosarcoma (OS) is the main primary bone cancer, presenting poor prognosis and difficult treatment. An innovative therapy may be found in cold plasmas, which show anti-cancer effects related to the generation of reactive oxygen and nitrogen species in liquids. In vitro models are based on the effects of plasma-treated culture media on cell cultures. However, effects of plasma-activated saline solutions with clinical application have not yet been explored in OS. The aim of this study is to obtain mechanistic insights on the action of plasma-activated Ringer’s saline (PAR) for OS therapy in cell and organotypic cultures. To that aim, cold atmospheric plasma jets were used to obtain PAR, which produced cytotoxic effects in human OS cells (SaOS-2, MG-63, and U2-OS), related to the increasing concentration of reactive oxygen and nitrogen species generated. Proof of selectivity was found in the sustained viability of hBM-MSCs with the same treatments. Organotypic cultures of murine OS confirmed the time-dependent cytotoxicity observed in 2D. Histological analysis showed a decrease in proliferating cells (lower Ki-67 expression). It is shown that the selectivity of PAR is highly dependent on the concentrations of reactive species, being the differential intracellular reactive oxygen species increase and DNA damage between OS cells and hBM-MSCs key mediators for cell apoptosis.
Highlights
Osteosarcoma (OS) is the most common primary malignant bone tumor and it mainly affects children, adolescents, and young adults
Two different plasma devices were employed in this work to treat Ringer’s saline and obtain plasma-activated Ringer’s saline (PAR); a single-electrode needle device operating in helium that will be designated as atmospheric pressure plasma jet (APPJ) and the kINPen, which is a pin-type electrode with a grounded outer electrode operating with Argon
Optical Emission Spectra were obtained for both plasma jets employing the same parameters of gas flow (1 L/min) and distance between the nozzle of the jet and the surface of the liquid (10 mm) during treatment of the Ringer’s saline (Figure 1A)
Summary
Osteosarcoma (OS) is the most common primary malignant bone tumor and it mainly affects children, adolescents, and young adults. It usually appears as an osteoid-producing solid tumor in the metaphysis of long bones, which experience rapid growth during childhood and adolescence [1]. Despite the low incidence of OS, it is ranked among the most frequent cause of cancer-related child death [2,3]. Current OS therapy consists in surgical resection of the tumor, combined with radiotherapy and/or systemic chemotherapy. Chemotherapeutic drugs have increased patient survival, this survival rate is still relatively low (50–60%) [4] and many patients develop drug-resistance [5].
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