ArticleJournal of orthopaedic translation2020
Apatinib ameliorates doxorubicin-induced migration and cancer stemness of osteosarcoma cells by inhibiting Sox2 via STAT3 signalling.
Article in Journal of orthopaedic translation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Antimetastatic Effects of aAntioxidants (Basel, Switzerland) · 2026Article
- The Role of Epithelial-Mesenchymal Transition in Osteosarcoma Progression: From Biology to Therapy.Diagnostics (Basel, Switzerland) · 2025Review
- Nitazoxanide alleviates CFA-induced rheumatoid arthritis in Wistar rats by modulating the STAT-3 and NF-κB pathways.Rheumatology and immunology research · 2025Article
- Role of tumor-derived exosomes and immune cells in osteosarcoma progression and targeted therapy.Frontiers in immunology · 2025Review
- Biomimetic Nano-delivery of Small-Molecule Piceatannol Modulates Tumor Stemness and Suppresses Colorectal Cancer Metastasis via Hippo/YAP1/SOX9 Signaling.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Zooming in and Out of Programmed Cell Death in Osteoarthritis: A Scientometric and Visualized Analysis.Journal of inflammation research · 2024Review
- miRNAs as short non-coding RNAs in regulating doxorubicin resistance.Journal of cell communication and signaling · 2023Review
- Self-Renewal and Pluripotency in Osteosarcoma Stem Cells' Chemoresistance: Notch, Hedgehog, and Wnt/β-Catenin Interplay with Embryonic Markers.International journal of molecular sciences · 2023Review
- Tumor-associated macrophages induce inflammation and drug resistance in a mechanically tunable engineered model of osteosarcoma.Biomaterials · 2023Article
- Pan-cancer analysis of PCAT6 and its effect on oesophageal squamous cell carcinoma cell proliferation and migration.Medical oncology (Northwood, London, England) · 2023Article
- Apatinib plus chemotherapy for non-metastatic osteosarcoma: a retrospective cohort study.Frontiers in oncology · 2023Article
- Multi-omics analysis based on 3D-bioprinted models innovates therapeutic target discovery of osteosarcoma.Bioactive materials · 2022Article
- Commentary: "Baicalein mediates the anti-tumor activity in Osteosarcoma through lncRNA-NEF driven Wnt/β-catenin signaling regulatory axis".Journal of orthopaedic translation · 2022Article
- Baicalein mediates the anti-tumor activity in Osteosarcoma through lncRNA-NEF driven Wnt/β-catenin signaling regulatory axis.Journal of orthopaedic translation · 2022Article
- Activity and safety of apatinib monotherapy or apatinib combined with chemotherapy for patients with metastatic or unresectable osteosarcoma over the age of 40 years: A retrospective analysis.Frontiers in oncology · 2022Article
- Stat3 Signaling Pathway: A Future Therapeutic Target for Bone-Related Diseases.Frontiers in pharmacology · 2022Review
- Biological evidence of cancer stem-like cells and recurrent disease in osteosarcoma.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Apatinib Functioned as Tumor Suppressor of Synovial Sarcoma through Regulating miR-34a-5p/HOXA13 Axis.Computational and mathematical methods in medicine · 2022Article
- Apatinib with doxorubicin and ifosfamide as neoadjuvant therapy for high-risk soft tissue sarcomas: a retrospective cohort study.Investigational new drugs · 2021Article
- Current research progress in targeted anti-angiogenesis therapy for osteosarcoma.Cell proliferation · 2021Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOsteosarcoma, ranking as the second primary cause of cancer-related death, is the most common type of bone cancer. Doxorubicin (DOX) is used as a first-line treatment for osteosarcoma; however, the tumour recurrence rate remains high. Recent studies have suggested that DOX-induced migration and stemness in osteosarcoma cells might be the primary reason of recurrence and drug resistance. However, the underlying mechanisms remain unclear. Therefore, it is urgent to explore novel effective treatments to overcome DOX-induced drug resistance of osteosarcoma.
methodsOsteosarcoma cells KHOS and U2OS were treated with DOX and apatinib (AP) alone or in combination. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays were performed to evaluate effects on proliferation. Flow cytometry analysis was carried out to assess cell apoptosis. Cell migration was determined by the transwell assay. Cancer stemness was detected by flow cytometry analysis of CD133
resultsHerein, we revealed that AP treatment significantly enhanced the sensitivity of osteosarcoma cells to DOX, reversed the DOX-induced stemness phenotype and metastasis capacity of osteosarcoma cells, and abolished the upregulation of p-STAT3, Sox2, Oct4, and Nanog. We further demonstrated that AP reversed DOX-induced stemness and migration of osteosarcoma cells through Sox2.
conclusionThese results suggested that AP significantly abolished the DOX-induced stemness phenotype and metastasis capacity in osteosarcoma cells by inhibiting Sox2 via STAT3 signalling. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our study indicates that Doxorubicin-based chemotherapeutics may simulate cancer stem cells (CSCs) properties in osteosarcoma, leading to the resistance of osteosarcoma. Apatinib can reduce the Doxorubicin-induced chemoresistance through STAT3/Sox2 pathway inactivation. This study represents that Apatinib may act as an effective chemotherapy sensitiser for reducing chemoresistance correlated with CSCs in osteosarcoma.
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