Background: Osteosarcoma, a tumor that originates from bone cells, has a poor prognosis and a high degree of malignancy. Anlotinib, a small-molecule multi-target tyrosine kinase inhibitor (TKI), is the first-line drug in treating osteosarcoma, especially in late-stage osteosarcoma. However, patients often develop resistance after using anlotinib for a certain period, which poses a challenge to its further clinical application. Recently, several TKIs, for instance regorafenib and cabozantinib, have showed clinical interest in treating osteosarcoma and target both vascular endothelial growth factor receptor (VEGFR) and mesenchymal epithelial transition factor (c-MET). Therefore, the identification of new TKI warrants further investigation.
Methods: We performed CCK8 aasays to confirm that BMS-794833 sensitization osteosarcoma cells to anlotinib. Bioinformatics analysis and rescue experiments showed that the reduce of resistance were dependent on the VEGFR/Ras/CDK2 pathway. Cell line based xenograft model were used to demonstrate that BMS-794833 and anlotinib could synergistically treat OS.
Results: Here, we found that BMS-794833 reduced anlotinib resistance in osteosarcoma by targeting the VEGFR/Ras/CDK2 pathway. CCK8 assay showed that BMS-794833 significantly improved the resistance of osteosarcoma cells to anlotinib. The results of rescue experiments showed that the regulatory effects of BMS-794833 on the proliferation and drug resistance of osteosarcoma cells were dependent on the VEGFR/Ras/CDK2 pathway. In addition, BMS-794833 affected the resistance of osteosarcoma cells to anlotinib through epithelial-mesenchymal transition (EMT) and apoptosis pathways. More importantly, BMS-794833 and anlotinib exerted synergistic therapeutic effects against osteosarcoma .
Conclusion: Altogether, this study reveals a new (VEGFR)-targeting drug that can be combined with anlotinib for the treatment of osteosarcoma, which provides an important theoretical basis for overcoming anlotinib resistance.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10963651 | PMC |
| http://dx.doi.org/10.1016/j.jbo.2024.100594 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
FOXR2 in cancer development: emerging player and therapeutic opportunities.
Oncol Res
January 2025
College of Food Sciences, Al-Qasim Green University, Babylon, Iraq.
Cancer, a leading cause of global mortality, remains a significant challenge to increasing life expectancy worldwide. Forkhead Box R2 (FOXR2), identified as an oncogene within the FOX gene family, plays a crucial role in developing various endoderm-derived organs. Recent studies have elucidated FOXR2-related pathways and their involvement in both tumor and non-tumor diseases.
View Article and Find Full Text PDFCurculigoside exhibits multiple therapeutic efficacy to induce apoptosis and ferroptosis in osteosarcoma via modulation of ROS and tumor microenvironment.
Tissue Cell
January 2025
Department of Orthopedics, Xijing Hospital, The Air Force Medical University, Xi'an 710032, China. Electronic address:
Objective: Patients with osteosarcoma (OS) exhibit metastasis upon diagnosis, and the condition frequently acquires resistance to traditional chemotherapy treatments, failing the therapy. The objective of this research was to examine the impact of curculigoside (Cur), a key phenolic compound discovered in the rhizome of C. orchioides Gaertn, on OS cells and the surrounding tumor environment.
View Article and Find Full Text PDFResearch Progress on Natural Products That Regulate miRNAs in the Treatment of Osteosarcoma.
Biology (Basel)
January 2025
Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China.
miRNAs are small non-coding RNA molecules that play critical roles in the regulation of gene expression and have been closely associated with various diseases, including cancer. These molecules significantly influence the cell cycle of tumor cells and control programmed cell death (apoptosis). Currently, research on miRNAs has become a major focus in developing cancer therapies.
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.
Forequarter amputation: a viable approach for salvaging lives in chemoresistant upper limb bone tumours.
BMJ Case Rep
January 2025
Orthopaedics, All India Institute of Medical Science - Bhopal, Bhopal, Madhya Pradesh, India.
This case revolves around a mid-childhood boy diagnosed with a chemoresistant chondroblastic osteosarcoma, a rare and aggressive form of bone tumour affecting his left proximal humerus. Histopathological confirmation of chondroblastic osteosarcoma was obtained through core-needle biopsy. Despite initiating cytoreductive neoadjuvant chemotherapy using a vincristine and cyclophosphamide regimen, the tumour exhibited resistance, prompting the decision to proceed with a forequarter amputation.
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!