ArticleJournal of Cancer2023
Dihydroartemisinin Potentiates VEGFR-TKIs Antitumorigenic Effect on Osteosarcoma by Regulating Loxl2/VEGFA Expression and Lipid Metabolism Pathway.
Article in Journal of Cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- A Review of Proteomic Studies in Uterine Leiomyosarcoma: Biomarkers, Pathways, and Clinical Potential.Current issues in molecular biology · 2026Review
- FGF-23 facilitates osteosarcoma metastasis by modulating the miR-4463/LOXL2 axis expression via the ERK, p38, and JNK signaling pathway.International journal of medical sciences · 2026Article
- Artemisinin and Its Derivatives from Molecular Mechanisms to Clinical Applications: New Horizons Beyond Antimalarials.International journal of molecular sciences · 2025Review
- Systemic strategies for osteosarcoma: advances and future directions.Discover oncology · 2025Review
- Multi-omics analysis reveals inhibition of osteosarcoma progression by sporoderm-removed Ganoderma lucidum spores via targeting glycerophospholipid and fatty acid metabolism.Scientific reports · 2025Article
- Phytochemical-Induced Metabolic Modulation: Dihydroartemisinin Regulates Cellular Metabolism in Madin-Darby Bovine Kidney Cells.International journal of molecular sciences · 2025Article
- Dihydroartemisinin inhibits lung cancer bone metastasis by modulating macrophage polarization.European journal of medical research · 2025Article
- Osteosarcoma immunometabolism: emerging mechanisms and clinical implications.Frontiers in immunology · 2025Review
- Targeting myeloid-derived suppressor cells in the tumor microenvironment: potential therapeutic approaches for osteosarcoma.Oncology research · 2025Review
- Artemisinin and Its Derivatives as Potential Anticancer Agents.Molecules (Basel, Switzerland) · 2024Review
- Review
- Lipid metabolism-derived FAAH is a sensitive marker for the prognosis and immunotherapy of osteosarcoma patients.Heliyon · 2024Article
- Targeted anti-angiogenesis therapy for advanced osteosarcoma.Frontiers in oncology · 2024Review
- LOXL2 in Cancer: A Two-Decade Perspective.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anti-angiogenesis therapy has shown significant anti-tumor effects against a variety of cancers. But resistance to antiangiogenic drugs, intrinsic and evasive, is frequently found in patients during treatment. Here, we report that dihydroartemisinin (DHA), a derivative of the Chinese medicine artemisinin, enhances antiangiogenic drug-induced cytotoxicity in osteosarcoma (OS) cells. Proteomics analysis revealed that DHA treatment significantly affected the activity of the collagen-modifying enzyme lysyl oxidase-like 2 (LOXL2), a regulatory gene associated with poor prognosis of OS. Furthermore, we found that DHA reduced the expression of vascular endothelial growth factor (VEGFA) by downregulating LOXL2. This mechanism was confirmed by QRT-PCR, western blot, and ELISA assays. Correspondingly, vector-enforced expression of LOXL2 markedly reduced VEGFA secretion. Untargeted metabolomic analysis revealed that the lipid metabolism that confers antiangiogenic drug resistance, was also interfered with by DHA. Thus, DHA not only exerts antitumor effects in OS cells directly but also synergizes with the antiangiogenic drug by regulating vascular endothelial growth factor A (VEGFA) expression and lipid metabolism.
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