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Updated: Feb 25, 2026
A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
Toosendanin demonstrates promising antitumor efficacy in osteosarcoma by targeting STAT3
1Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Signal transducer and activator of transcription 3(STAT3) is an emerging target for cancer therapy. In this study, we identify Toosendanin (TSN) is an effective inhibitor of STAT3, leading to the impediment of various oncogenic processes in osteosarcoma. TSN selectively inactivates phospho-STAT3 (Tyr-705); subsequent molecular docking and in vitro SPR analysis uncover TSN directly binds to the SH2 domain of STAT3. Consequently, TSN blocks STAT3 dimerization and impairs the complex formation of STAT3 and epidermal growth factor receptor (EGFR). In an animal tumor model study, TSN is well tolerated, inhibits osteosarcoma growth and metastasis. In another osteosarcoma patient-derived xenografts (PDX) model, we find TSN triggers strong inhibitory effects on patient-derived tumors. Further studies show that TSN also displays activity against other solid tumors. Our preclinical work therefore supports that TSN acts as a novel inhibitor of STAT3 that blocks tumorigenesis in ostoesarcoma.
Insights
Toosendanin (TSN) effectively inhibits Signal Transducer and Activator of Transcription 3 (STAT3) in osteosarcoma. This novel STAT3 inhibitor blocks tumor growth and metastasis, showing promise for cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Signal transducer and activator of transcription 3 (STAT3) is a key regulator in various cancers, making it a promising therapeutic target.
- Osteosarcoma is a challenging bone cancer with limited effective treatment options.
Purpose of the Study:
- To investigate Toosendanin (TSN) as a novel inhibitor of STAT3 signaling in osteosarcoma.
- To elucidate the mechanism of action of TSN on STAT3 and its downstream effects on oncogenic processes.
Main Methods:
- Molecular docking and surface plasmon resonance (SPR) assays to determine TSN's binding site on STAT3.
- In vitro studies to assess the effect of TSN on STAT3 phosphorylation and dimerization.
- In vivo studies using animal tumor models and patient-derived xenografts (PDX) to evaluate TSN's efficacy and tolerability.
Main Results:
- TSN selectively inactivates phospho-STAT3 (Tyr-705) by directly binding to the SH2 domain of STAT3.
- TSN inhibits STAT3 dimerization and its complex formation with epidermal growth factor receptor (EGFR).
- TSN demonstrates significant inhibition of osteosarcoma growth and metastasis in preclinical models, including PDX models, and shows activity against other solid tumors.
Conclusions:
- TSN is a potent inhibitor of STAT3 signaling with significant preclinical efficacy in osteosarcoma.
- TSN's ability to block STAT3 dimerization and downstream oncogenic pathways supports its potential as a novel cancer therapeutic agent.
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