Background: In the widespread adoption of chemotherapy, drug resistance has been the major obstacle to tumor elimination in cancer patients. Our aim was to explore the role of TGF-β in osteosarcoma-associated chemoresistance.
Methods: We performed a cytotoxicity analysis of methotrexate (MTX) and cisplatin (CIS) in TGF-β-treated osteosarcoma cells. Then, the metabolite profile of the core metabolic energy pathways in Saos-2 and MG-63 cell extracts was analyzed by H-NMR. We detected the expression of succinate dehydrogenase (SDH), STAT1, and hypoxia-inducible factor 1α (HIF1α) in TGF-β-treated osteosarcoma cells and further tested the effects of these molecules on the cytotoxicity induced by chemotherapeutic agents. Using in vivo experiments, we examined the tumor growth and survival time of Saos-2-bearing mice treated with a combination of chemotherapeutic agents and a HIF1α inhibitor.
Results: The metabolic analysis revealed enhanced succinate production in osteosarcoma cells after TGF-β treatment. We further found a decrease in SDH expression and an increase in HIF1α expression in TGF-β-treated osteosarcoma cells. Consistently, blockade of SDH efficiently enhanced the resistance of Saos-2 and MG-63 cells to MTX and CIS. Additionally, a HIF1α inhibitor significantly strengthened the anticancer efficacy of the chemotherapeutic drugs in mice with osteosarcoma cancer.
Conclusion: Our study demonstrated that TGF-β attenuated the expression of SDH by reducing the transcription factor STAT1. The reduction in SDH then caused the upregulation of HIF1α, thereby rerouting glucose metabolism and aggravating chemoresistance in osteosarcoma cells. Linking tumor cell metabolism to the formation of chemotherapy resistance, our study may guide the development of additional treatments for osteosarcoma.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582194 | PMC |
| http://dx.doi.org/10.1186/s12885-021-08954-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Deciphering the oncogenic network: how C1QTNF1-AS1 modulates osteosarcoma through miR-34a-5p and glycolytic pathways.
Front Oncol
January 2025
Department of Minimally Invasive Spine Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, China.
Introduction: Osteosarcoma (OS), a prevalent metastatic cancer among young individuals, is associated with a grim prognosis. Long non-coding RNAs (lncRNAs), including C1QTNF1-AS1, are pivotal regulators of cancer cell proliferation and motility. As an oncogene, C1QTNF1-AS1 is implicated in various tumor types, such as colorectal, pancreatic, hepatocellular carcinomas, and OS.
View Article and Find Full Text PDFUsing β-Elemene to reduce stemness and drug resistance in osteosarcoma: A focus on the AKT/FOXO1 signaling pathway and immune modulation.
J Bone Oncol
February 2025
Department of Endocrinology, The Central Hospital of Ezhou, Ezhou 436000, China.
Objective: Osteosarcoma, a highly malignant bone tumor, poses significant treatment challenges due to its propensity for stemness and drug resistance, particularly against doxorubicin (DOX). This study aims to investigate the mechanism by which β-elemene reduces the stemness of osteosarcoma stem cells and ultimately decreases DOX resistance by inhibiting the Akt/FoxO1 signaling pathway and activating a macrophage-mediated inflammatory microenvironment.
Methods: Osteosarcoma stem cells were isolated and induced for DOX resistance.
Combined Graphene Oxide with 2-Methoxyestradiol for Effective Anticancer Therapy in-vitro Model.
Int J Nanomedicine
January 2025
Department of Medical Chemistry, Faculty of Medicine, Medical University of Gdansk, Gdansk, Poland.
Introduction: This article describes the invention of graphene oxide (GO) or reduced graphene oxide (rGO) functionalised with 2-methoxy estradiol. The presence of polar hydroxyl groups enables the binding of 2-ME to GO/rGO through hydrogen bonds with epoxy and hydroxyl groups located on the surface and carbonyl and carboxyl groups located at the edges of graphene flake sheets.
Methods: The patented method of producing the subject of the invention and the research results regarding its anticancer effectiveness via cytotoxicity in an in vivo model (against A375 melanoma and 143B osteosarcoma cells) are described.
An annotated high-content fluorescence microscopy dataset with EGFP-Galectin-3-stained cells and manually labelled outlines.
Data Brief
February 2025
Cell Death, Lysosomes and Artificial Intelligence Group, Department of Experimental Medical Science, Faculty of Medicine, Lund University, BMC D10, 22184 Lund, Sweden.
Many forms of bioimage analysis involve the detection of objects and their outlines. In the context of microscopy-based high-throughput drug and genomic screening and even in smaller scale microscopy experiments, the objects that most often need to be detected are cells. In order to develop and benchmark algorithms and neural networks that can perform this task, high-quality datasets with annotated cell outlines are needed.
View Article and Find Full Text PDFC1GALT1 expression predicts poor survival in osteosarcoma and is crucial for ABCC1 transporter-mediated doxorubicin resistance.
J Pathol
January 2025
Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
Osteosarcoma is an aggressive bone malignancy with a high propensity for drug resistance and metastasis, leading to poor clinical outcomes. This study investigates the role of core 1 β1,3-galactosyltransferase 1 (C1GALT1) in osteosarcoma, focusing on its implications in chemoresistance. Our findings reveal that high expression of C1GALT1 is associated with advanced stages, adverse overall survival, and increased recurrence rates.
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!