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Updated: Feb 4, 2026
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Inhibition of STAT3 blocks protein synthesis and tumor metastasis in osteosarcoma cells
Dongqing Zuo1,2, Kristen L Shogren1, Jie Zang3
1Department of Orthopedic Surgery, 2-69 Medical Sciences, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA.
Background:
Osteosarcoma is the most common bone cancer. Despite advances, molecular mechanisms associated with osteosarcoma have not been fully understood. Hence, an effective treatment for osteosarcoma has yet to be developed. Even though signal transducer and activator of transcription3 (STAT3) has been implicated, its role in pathogenesis of osteosarcoma is not fully determined. In this study, we investigated the antitumor effect of napabucasin (NP) (BBI608), an inhibitor of STAT3 on osteosarcoma in vitro and in vivo and studied the underlying molecular mechanism.
Methods:
Cell viability, colony formation, apoptosis, tumor growth and metastasis assays were performed to examine the effect of NP on osteosarcoma in vitro and in vivo. Real-time RT-PCR, western analysis, immunofluorescence and reporter assays were used to monitor the expression and activity of proteins and underlying molecular pathways. Protein synthesis, co-immunoprecipitation and CAP binding assays were carried out to understand NP-mediated mechanism of actions in osteosarcoma cells.
Results:
Our results show that NP treatment decreases cell viability and induces apoptosis in several osteosarcoma cell lines. NP treatment suppresses both expression and phosphorylation of STAT3 in addition to blocking STAT3-mediated transcription and downstream target proteins in osteosarcoma cells. Furthermore, NP inhibits protein synthesis through regulation of the eukaryotic initiation factor 4E (eIF4E) and eIF4E-binding protein 1 (4E-BP1). NP also inhibits the progression of osteosarcoma tumors and metastasis in vivo in an orthotopic tibial model of osteosarcoma.
Conclusions:
Taken together, our investigation reveals that NP acts through a novel mechanism and inhibits osteosarcoma growth and metastasis, and could be investigated clinically for treating osteosarcoma patients alone or in combination with other drugs.
Insights
Napabucasin (NP), a STAT3 inhibitor, effectively reduces osteosarcoma cell viability and metastasis. This novel mechanism targeting STAT3 and protein synthesis offers potential for new osteosarcoma treatments.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Osteosarcoma remains a significant challenge due to poorly understood molecular mechanisms.
- Signal transducer and activator of transcription 3 (STAT3) is implicated in osteosarcoma pathogenesis, but its precise role requires further elucidation.
- Developing effective treatments for osteosarcoma is critical.
Purpose of the Study:
- To investigate the antitumor effects of napabucasin (NP), a STAT3 inhibitor, on osteosarcoma.
- To elucidate the molecular mechanisms underlying NP's action in osteosarcoma.
- To evaluate NP's efficacy in vitro and in vivo.
Main Methods:
- Assessed cell viability, colony formation, and apoptosis in osteosarcoma cell lines treated with NP.
- Utilized real-time RT-PCR, western analysis, immunofluorescence, and reporter assays to monitor STAT3 expression and activity.
- Performed in vivo tumor growth and metastasis assays in an orthotopic osteosarcoma model.
Main Results:
- NP treatment significantly decreased osteosarcoma cell viability and induced apoptosis.
- NP suppressed STAT3 expression, phosphorylation, and downstream transcriptional activity.
- NP inhibited protein synthesis by regulating eukaryotic initiation factor 4E (eIF4E) and 4E-binding protein 1 (4E-BP1).
- NP demonstrated efficacy in inhibiting tumor growth and metastasis in vivo.
Conclusions:
- Napabucasin exhibits a novel mechanism of action against osteosarcoma by inhibiting STAT3 and protein synthesis.
- NP effectively suppresses osteosarcoma growth and metastasis.
- NP warrants further clinical investigation as a potential therapeutic agent for osteosarcoma, alone or in combination therapy.
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