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Updated: Feb 25, 2026

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Decrease in stathmin expression by arsenic trioxide inhibits the proliferation and invasion of osteosarcoma cells via
1Clinical Laboratory, The Children's Hospital of Suzhou University, Suzhou, Jiangsu 215025, P.R. China.
Abstract:
Osteosarcoma (OS) is the most common type of malignant bone tumor in children and adolescents. In total, 40-50% of patients with OS experience metastasis, and thus have a poor prognosis. Our previous study demonstrated that arsenic trioxide (As2O3) combined with doxorubicin [also known as Adriamycin (ADM)] significantly inhibited OS cell proliferation by downregulating stathmin expression. The present study investigated the effect and mechanism of stathmin expression on OS cell invasion. It was identified that the expression of stathmin was increased in human ADM-resistant OS MG63 (MG63/dox) cells compared with the level in the normal osteoblast hFoB1.19cell line using western blot analysis. Lentiviral-mediated small hairpin RNA (shRNA) was constructed to silence stathmin expression of MG63/dox cells. In transwell assay, stathmin-knockdown significantly suppressed migration and invasion in MG63/dox cells. As2O3 combined with ADM inhibited the migration and invasion of MG63/dox cells, and was associated with the downregulation of phosphorylated-mitogen-activated protein kinase (MAPK) 1 and β-catenin, and upregulation of phosphorylated-MAPK8 and E-cadherin. In addition, stathmin-knockdown significantly suppressed tumor growth and increased E-cadherin expression in a xenograft nude mouse model. Taken together, these data suggested that As2O3 combined with ADM inhibited stathmin-mediated invasion via the MAPK pathway. Elucidation of the mechanism for stathmin downregulation by As2O3 may provide novel insights into the mechanism of OS metastasis.
Insights
Arsenic trioxide and doxorubicin combination therapy inhibits osteosarcoma (OS) cell invasion by downregulating stathmin. This treatment targets the MAPK pathway, offering new insights into OS metastasis mechanisms.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Osteosarcoma (OS) is a common pediatric bone cancer with high metastasis rates.
- Stathmin expression is implicated in cancer cell proliferation and invasion.
- Adriamycin (ADM)-resistant OS cells exhibit increased stathmin levels.
Purpose of the Study:
- To investigate the role of stathmin in osteosarcoma cell invasion.
- To elucidate the mechanism by which arsenic trioxide (As2O3) and ADM inhibit OS metastasis.
Main Methods:
- Western blot analysis to assess stathmin expression.
- Lentiviral-mediated shRNA to silence stathmin.
- Transwell assays to evaluate cell migration and invasion.
- Xenograft nude mouse models to assess tumor growth in vivo.
Main Results:
- Stathmin knockdown significantly suppressed migration and invasion in ADM-resistant OS cells.
- As2O3 combined with ADM inhibited OS cell migration and invasion.
- The combination treatment modulated MAPK signaling pathways and E-cadherin expression.
- Stathmin knockdown reduced tumor growth and increased E-cadherin in vivo.
Conclusions:
- As2O3 and ADM inhibit stathmin-mediated osteosarcoma invasion through the MAPK pathway.
- Targeting stathmin offers a potential therapeutic strategy for OS metastasis.
- Understanding stathmin's role provides insights into OS progression and treatment.
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