Related Experiment Video
Updated: May 19, 2026
Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
SC-1, a sorafenib derivative, shows anti-tumor effects in osteogenic sarcoma cells
Chen-Ti Wang1, Chen-Si Lin, Chung-Wai Shiau
1Department of Orthopedics, National Taiwan University Hospital, Taipei, Taiwan.
Abstract:
Despite significant advances in the treatment of osteosarcoma (OS), overall survival rate of OS patients has remained relatively constant for over two decades and novel approaches are needed to further improve prognosis. Here, we report the anti-tumor effect of SC-1, a novel sorafenib derivative that closely resembles sorafenib structurally but is devoid of kinase inhibitory activity, on OS cells through mediation of signal transducer and activator of transcription 3 (STAT3). SC-1 showed similar effects to sorafenib on growth inhibition and apoptosis, and downregulated phospho-STAT3 (p-STAT3) at tyrosine 705 in all tested OS cell lines (U2OS, HOS, and 143B). Expression of STAT3-driven genes, including cylcin D1 and c-myc, were also repressed by SC-1. Ectopic expression of STAT3 in 143B cells abolished apoptosis in SC-1-treated cells. Inhibition of SHP-1 decreased SC-1-induced apoptosis. SC-1 upregulated the activity of SHP-1 in tested OS cell lines in a dose-dependent manner. Finally, SC-1 reduced 143B tumor growth significantly in vivo, which was associated with downregulation of p-STAT3 and upregulation of SHP-1 activity. These data demonstrate that SC-1 has clinical potential for the treatment of OS patients.
Insights
A novel sorafenib derivative, SC-1, effectively inhibits osteosarcoma growth and induces apoptosis by targeting signal transducer and activator of transcription 3 (STAT3) signaling. SC-1 shows significant potential for treating osteosarcoma patients.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Osteosarcoma (OS) treatment has stagnated, necessitating novel therapeutic strategies.
- Signal transducer and activator of transcription 3 (STAT3) is implicated in OS progression.
Purpose of the Study:
- To investigate the anti-tumor effects of SC-1, a novel sorafenib derivative, on osteosarcoma cells.
- To elucidate the mechanism of SC-1 action, focusing on STAT3 and SHP-1 pathways.
Main Methods:
- SC-1's effects on OS cell lines (U2OS, HOS, 143B) were assessed for growth inhibition and apoptosis.
- Phospho-STAT3 (p-STAT3) levels and STAT3-driven gene expression were analyzed.
- SHP-1 activity was measured, and STAT3 overexpression/SHP-1 inhibition were performed.
- In vivo studies evaluated SC-1's efficacy in reducing tumor growth.
Main Results:
- SC-1 induced growth inhibition and apoptosis in OS cells, similar to sorafenib.
- SC-1 downregulated p-STAT3 and STAT3-driven genes (cyclin D1, c-myc).
- SC-1 upregulated SHP-1 activity and its inhibition reduced SC-1-induced apoptosis.
- SC-1 significantly inhibited tumor growth in vivo, associated with p-STAT3 downregulation and SHP-1 upregulation.
Conclusions:
- SC-1 demonstrates potent anti-tumor activity against osteosarcoma through STAT3 and SHP-1 modulation.
- SC-1 exhibits significant clinical potential for osteosarcoma treatment.
