Combination of electroporation delivered metabolic modulators with low-dose chemotherapy in osteosarcoma

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Gill, Kheshwant S.
Fernandes, Philana
Bird, Brian
Soden, Declan M.
Forde, Patrick F.
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Background: Osteosarcoma accounts for roughly 60% of all malignant bone tumors in children and young adults. The five-year survival rate for localized tumors after surgery and chemotherapy is approximately 70% whilst it drastically reduces to 15–30% in metastatic cases. Metabolic modulation is known to increase sensitivity of cancers to chemotherapy. A novel treatment strategy in Osteosarcoma is needed to battle this devastating malady. Results: Electroporation-delivered metabolic modulators were more effective in halting the cell cycle of Osteosarcoma cells and this negatively affects their ability to recover and proliferate, as shown in colony formation assays. Electroporation-delivered metabolic modulators increase the sensitivity of Osteosarcoma cells to chemotherapy and this combination reduces their survivability. Conclusion: This novel treatment approach highlights the efficacy of electroporation in the delivery of metabolic modulators in Osteosarcoma cells, and increased sensitivity to chemotherapy allowing for a lower dose to be therapeutic. Methods: Metabolic modulations of two Osteosarcoma cell lines were performed with clinically available modulators delivered using electroporation, and its combination with low-dose Cisplatin. The effects of Dicholoroacetic acid, 2-Deoxy-D-glucose and Metformin on cell cycle and recovery of Osteosarcoma cells were assessed. Their sensitivity to chemotherapy was also assessed when treated in combination with electroporation-delivered metabolic modulators.
Osteosarcoma , Electroporation , Metabolic modulation , Cell cycle , Combination treatment
Gill, K. S., Fernandes, P., Bird, B., Soden, D. M. and Forde, P. F. (2018) 'Combination of electroporation delivered metabolic modulators with low-dose chemotherapy in osteosarcoma', Oncotarget, 9(59), pp. 31473-31489. doi: 10.18632/oncotarget.25843