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Updated: Apr 14, 2026
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
LY2109761 inhibits metastasis and enhances chemosensitivity in osteosarcoma MG-63 cells
1Department of Spine, The Affiliated Hospital of Qingdao University, Qingdao, China. renxuanfengqd@126.com.
Objective:
Studies have shown that transforming growth factor-beta (TGF-β) is associated with metastasis and chemoresistance of osteosarcoma. The TGF-β kinase inhibitor LY2109761 could inhibits metastasis and enhances chemosensitivity in several cancers, but its role and mechanisms in osteosarcoma (OS) is unclear. Here, we investigated the role and mechanism of LY2109761 on metastasis and chemosensitivity of OS MG-63 cells.
Materials And Methods:
MG-63 cells were treated with LY2109761 or/and cisplatin. The cell viability and apoptosis of MG-63 cells were detected by MTT and ELISA. Matrigel invasion assay was used to detect cell invasion in vitro. pSMAD2 and S100A4 was detected by western blot assay. Furthermore, the efficacy of LY2109761 combined with S100A4 cDNA plaismid transfection on cell viability, apoptosis and chemosensitivity to cisplatin in OS MG-63 cells was further examined.
Results:
LY2109761 was sufficient to induce apoptosis and inhibited growth of MG-63 cells in vitro. Combination with LY2109761 significantly augmented the cytotoxicity of cisplatin in MG-63 cells. LY2109761 significantly inhibited invasion of MG-63 cells in vitro. The LY2109761-induced increase in cell apoptosis and the cytotoxicity of cisplatin, and decrease in cell invasion was blocked completely when S100A4 expression was restored in the MG-63 cells by S100A4 cDNA plasmid transfection.
Conclusions:
Our data indicate that LY2109761 suppresses OS metastasis and enhanced chemosensitivity by targeting S100A4. LY2109761 may have important implications for the development of strategies for inhibiting metastasis and overcoming OS cell resistance to chemotherapy.
Insights
The TGF-β kinase inhibitor LY2109761 suppresses osteosarcoma (OS) metastasis and enhances chemosensitivity by targeting S100A4. This suggests LY2109761 could be a promising therapeutic strategy for OS treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Transforming growth factor-beta (TGF-β) signaling is implicated in osteosarcoma (OS) metastasis and chemoresistance.
- The TGF-β kinase inhibitor LY2109761 shows potential in various cancers but its role in OS remains unclear.
Purpose of the Study:
- To investigate the role and mechanism of LY2109761 in regulating metastasis and chemosensitivity in OS MG-63 cells.
- To determine if LY2109761 affects S100A4 expression in OS cells.
Main Methods:
- MG-63 cells were treated with LY2109761 and/or cisplatin.
- Cell viability, apoptosis, and invasion were assessed using MTT, ELISA, and Matrigel assays.
- Western blot was used to detect pSMAD2 and S100A4 expression. S100A4 cDNA plasmid transfection was employed to restore S100A4 expression.
Main Results:
- LY2109761 induced apoptosis, inhibited MG-63 cell growth, and reduced invasion in vitro.
- Combined treatment with LY2109761 and cisplatin significantly enhanced cytotoxicity.
- Restoring S100A4 expression blocked the effects of LY2109761 on apoptosis, chemosensitivity, and invasion.
Conclusions:
- LY2109761 suppresses osteosarcoma metastasis and enhances chemosensitivity by targeting S100A4.
- LY2109761 holds potential for developing novel therapeutic strategies against osteosarcoma metastasis and chemoresistance.
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