Spheroid‐based 3D cell cultures identify salinomycin as a promising drug for the treatment of chondrosarcoma

Abstract

Chondrosarcoma (CS) is a cartilage malignancy of adulthood that is treated by surgery alone, since chemotherapy is considered ineffective. Unfortunately, a large proportion of patients with CS develop lung metastases, and several die of the disease. In this study, we compared 3D-spheroid cultures and conventional cell monolayer models in order to identify the best way to select anticancer agents that could be effective for the systemic control of CS. Using SW1353 cells, we developed a three-dimensional (3D) in vitro culture model to mimic in vivo features of CS microenvironment and evaluated the efficacy of different drugs to modulate CS cell proliferation and survival in 2D versus 3D-cultures. Doxorubicin (DXR) and cisplatin, that are widely employed in sarcomas, were less effective on 3D-CS spheroids when compared to standard monolayer models, whereas treatment with the ionophore salinomycin (SAL) had a strong cytotoxic effect both on 2D and 3D-cultures. Furthermore, as demonstrated by the reduced viability and the enhanced DXR nuclear localization, SAL enhanced DXR cytotoxicity in 3D-CS spheroids also at sub-lethal doses. SAL activity on 3D-CS spheroids was mediated by a significant induction of apoptosis via caspase activation. This study demonstrates that preclinical tests significantly differ in monolayer and 3D cultures of CS cells. Using this approach, SAL, alone or, at sub-lethal concentrations, in combination with DXR, represents a promising agent for the systemic treatment of CS. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Selection of Effective Therapies Using Three-Dimensional in vitro Modeling of Chondrosarcoma

“…To date, chondrosarcoma cell lines have been cultured in 3D using non-adherent surfaces (van Oosterwijk et al, 2012b), the hanging drop method (Perut et al, 2018), collagen scaffolds (Truong et al, 2012;Hamdi et al, 2015) and alginate beads (Lhuissier et al, 2017). The attachment prevention techniques used succeeded in formation of large regular multicellular tumor spheroids (MCTS) with corresponding representative regions of quiescence, hypoxia and necrosis, whereas cells within the collagen gel model migrated throughout the gel and oxygen levels were regulated externally in order to mimic in vivo hypoxic circumstances (van Oosterwijk et al, 2012b;Hamdi et al, 2015).…”

Spheroids as a Type of Three-Dimensional Cell Cultures—Examples of Methods of Preparation and the Most Important Application

“…Perut et al (2018) compared the effects of anticancer drugs on human chondrosarcoma (SW1353) and osteosarcoma (MG-63DXR30 cell line obtained from parental MG-63) cell lines [ 20 ].…”

Scaffold-free and label-free biofabrication technology using levitational assembly in a high magnetic field

“…In this study we selected the human chondrosarcoma cell line SW1353 as a reliable well-characterized human cell source for fabrication of tissue spheroids [24][25][26]. The employed fabrication method enabled the formation of tissue spheroids with regular sizes and shapes, which is essential for the standardization of magnetic levitation assembly experiments, as well as for the estimation of the possible toxicity of a high magnetic field and paramagnetic medium ( figure 4(a)).…”