ArticleInvestigational new drugs2021
Notoginsenoside R1 counteracts mesenchymal stem cell-evoked oncogenesis and doxorubicin resistance in osteosarcoma cells by blocking IL-6 secretion-induced JAK2/STAT3 signaling.
Article in Investigational new drugs, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Research progress of ginseng active ingredients combined with chemotherapy in cancer therapy.Journal of ginseng research · 2026Review
- Mechanism of Saikosaponin D in regulating ferroptosis in patient-derived lung adenocarcinoma organoids via upregulation of ATF3/CHOP/CHAC1 signaling.Scientific reports · 2026Article
- The Multitalented Marvels: Exploring the Versatile Potential of Natural Products in Osteosarcoma Treatment.Cancer informatics · 2026Review
- [Ecliptasaponin A ameliorates DSS-induced colitis in mice by suppressing M1 macrophage polarizationNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Microenvironment matters: insights from the FOSTER consortium on microenvironment-driven approaches to osteosarcoma therapy.Cancer metastasis reviews · 2025Review
- Suppression of JAK2/STAT3 Pathway by Notoginsenoside R1 Reduces Epithelial-Mesenchymal Transition in Non-small Cell Lung Cancer.Molecular biotechnology · 2025Article
- The malignant dialogue between cancer-associated fibroblasts and osteosarcoma cells: microenvironment-mediated drug resistance and therapeutic targets.Frontiers in immunology · 2025Review
- Super-enhancer-driven LIF promotes the mesenchymal transition in glioblastoma by activating ITGB2 signaling feedback in microglia.Neuro-oncology · 2024Article
- Improving targeted small molecule drugs to overcome chemotherapy resistance.Cancer reports (Hoboken, N.J.) · 2024Review
- Overexpression of miR-506-3p reversed doxorubicin resistance in drug-resistant osteosarcoma cells.Frontiers in pharmacology · 2024Article
- miRNAs as short non-coding RNAs in regulating doxorubicin resistance.Journal of cell communication and signaling · 2023Review
- Exploring the potential use of Chinese herbs in regulating the inflammatory microenvironment of tumours based on the concept of 'state-target identification and treatment': a scooping review.Chinese medicine · 2023Review
- Acute myeloid leukemia (AML)-derived mesenchymal stem cells induce chemoresistance and epithelial-mesenchymal transition-like program in AML through IL-6/JAK2/STAT3 signaling.Cancer science · 2023Article
- 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
- Notoginsenoside R1 relieves the myocardial infarction via activating the JAK2/STAT3 signaling pathway in vivo and in vitro.Bioengineered · 2022Article
- Mesenchymal Stem Cells and Extracellular Vesicles in Osteosarcoma Pathogenesis and Therapy.International journal of molecular sciences · 2021Review
- Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery.Antioxidants (Basel, Switzerland) · 2021Review
- The Role of Tumor-Stroma Interactions in Drug Resistance Within Tumor Microenvironment.Frontiers in cell and developmental biology · 2021Review
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Authors and funding
6 authors at 2 institutions in 1 country.
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Abstract
Tumor microenvironment is a critical participant in the initiation, progression and drug resistance of carcinomas, including osteosarcoma. Notoginsenoside R1 (NGR1) is a proverbial active ingredient of the traditional Chinese medicine Panax notoginseng (PN) and possess undeniable roles in several cancers. Nevertheless, its function in osteosarcoma and tumor microenvironment remains elusive. In the current study, exposure to NGR1 dose-dependently inhibited osteosarcoma cell viability and migration, and induced apoptosis. Furthermore, osteosarcoma cells that were incubated with conditioned medium (CM) from bone marrow mesenchymal stem cells (BMSCs) exhibited greater proliferation, migration capacity and MMP-2 and MMP-9 expression relative to control cells, which was reversed when BMSCs were treated with NGR1. Notably, administration with NGR1 antagonized CM-evoked doxorubicin resistance in osteosarcoma cells by decreasing cell viability and increasing cell apoptosis and caspase-3/9 activity. Mechanically, NGR1 suppressed IL-6 secretion from BMSCs, as well as the subsequent activation of the JAK2/STAT3 signaling in osteosarcoma cells. In addition, blocking the JAK2 pathway by its antagonist AG490 reversed CM-induced osteosarcoma cell proliferation, migration and doxorubicin resistance. Moreover, exogenous supplementation with IL-6 engendered not only the reactivation of the JAK2/STAT3 signaling but also muted NGR1-mediated efficacy against osteosarcoma cell malignancy and doxorubicin resistance. Collectively, NGR1 may directly restrain osteosarcoma cell growth and migration, or indirectly antagonize MSC-evoked malignancy and drug resistance by interdicting IL-6 secretion-evoked activation of the JAK2/STAT3 pathway. Consequently, the current study may highlight a promising therapeutic strategy against osteosarcoma by regulating tumor cells and the tumor microenvironment.
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