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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101145 | PMC |
| http://dx.doi.org/10.18632/oncotarget.25843 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Exploring TNFR1: from discovery to targeted therapy development.
J Transl Med
January 2025
School of Medicine, Shanghai Baoshan Luodian Hospital, Shanghai University, Shanghai, 201908, China.
This review seeks to elucidate the therapeutic potential of tumor necrosis factor receptor 1 (TNFR1) and enhance our comprehension of its role in disease mechanisms. As a critical cell-surface receptor, TNFR1 regulates key signaling pathways, such as nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK), which are associated with pro-inflammatory responses and cell death. The intricate regulatory mechanisms of TNFR1 signaling and its involvement in various diseases, including inflammatory disorders, infectious diseases, cancer, and metabolic syndromes, have attracted increasing scholarly attention.
View Article and Find Full Text PDFIntegrating single-cell RNA-Seq and bulk RNA-Seq data to explore the key role of fatty acid metabolism in hepatocellular carcinoma.
Sci Rep
January 2025
Department of Emergency, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
Hepatocellular carcinoma (HCC) is a predominant cause of cancer-related mortality globally, noted for its propensity towards late-stage diagnosis and scarcity of effective treatment modalities. The process of metabolic reprogramming, with a specific emphasis on lipid metabolism, is instrumental in the progression of HCC. Nevertheless, the precise mechanisms through which lipid metabolism impacts HCC and its viability as a therapeutic target have yet to be fully elucidated.
View Article and Find Full Text PDFCytotoxic mechanisms of pemetrexed and HDAC inhibition in non-small cell lung cancer cells involving ribonucleotides in DNA.
Sci Rep
January 2025
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, N-7491, Trondheim, Norway.
The cytotoxic mechanisms of thymidylate synthase inhibitors, such as the multitarget antifolate pemetrexed, are not yet fully understood. Emerging evidence indicates that combining pemetrexed with histone deacetylase inhibitors (HDACi) may enhance therapeutic efficacy in non-small cell lung cancer (NSCLC). To explore this further, A549 NSCLC cells were treated with various combinations of pemetrexed and the HDACi MS275 (Entinostat), and subsequently assessed for cell viability, cell cycle changes, and genotoxic markers.
View Article and Find Full Text PDFMutated IL-32θ (A94V) inhibits COX2, GM-CSF and CYP1A1 through AhR/ARNT and MAPKs/NF-κB/AP-1 in keratinocytes exposed to PM.
Sci Rep
January 2025
Department of Bioscience and Biotechnology, Konkuk University, Seoul, 05029, Republic of Korea.
Exposure to particulate matter (PM) in the air harms human health. Most studies on particulate matter's (PM) effects have primarily focused on respiratory and cardiovascular diseases. Recently, IL-32θ, one of the IL-32 isoforms, has been demonstrated to modulate cancer development and inflammatory responses.
View Article and Find Full Text PDFSingle-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis.
Nat Commun
January 2025
Interfakultäres Institut für Biochemie, University of Tübingen, Tübingen, Germany.
A balanced activity of cGMP signaling contributes to the maintenance of cardiovascular homeostasis. Vascular smooth muscle cells (VSMCs) can generate cGMP via three ligand-activated guanylyl cyclases, the NO-sensitive guanylyl cyclase, the atrial natriuretic peptide (ANP)-activated GC-A, and the C-type natriuretic peptide (CNP)-stimulated GC-B. Here, we study natriuretic peptide signaling in murine VSMCs and atherosclerotic lesions.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!