Combination of electroporation delivered metabolic modulators with low-dose chemotherapy in osteosarcoma
Metrics: PDF 554 views | HTML 1479 views | ?
Kheshwant S. Gill1, Philana Fernandes1, Brian Bird1,2, Declan M. Soden1 and Patrick F. Forde1
1Cancer Research at UCC, Western Gateway Building, University College Cork, Cork, Ireland
2Bons Secours Hospital, Cork, Ireland
Patrick F. Forde, email: firstname.lastname@example.org
Keywords: osteosarcoma; electroporation; metabolic modulation; cell cycle; combination treatment
Received: February 03, 2018 Accepted: July 08, 2018 Published: July 31, 2018
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.