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Updated: Dec 19, 2025
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Sunitinib inhibits PD-L1 expression in osteosarcoma by targeting STAT3 and remodels the immune system in
Xian Liang Duan1, Jian Ping Guo1, Fan Li1
1The Second Department of Orthopedic, The Affiliated Hospital of Beihua University, Jilin 132011, PR China.
Abstract:
Aim: Exploring the mechanisms of the combination therapy using VEGFR-TKI and immune checkpoint inhibitors might be useful to control the development of osteosarcoma. Materials & methods: The expression of PD-L1 and STAT3 in osteosarcoma were determined with western blot. Proliferation, migration and invasion were determined with CCK-8 and Transwell assays. Lung metastases, tumor growth, survival and immune cell populations were performed in tumor-bearing mice. Results: Sunitinib reduced the expression of PD-L1 by inhibiting the activation of STAT3 and suppressed the migration and invasion in osteosarcoma cells. Combination therapy reduced lung metastases, tumor growth, improved survival and reverse tumor microenvironment in tumor-bearing mice. Conclusion: Sunitinib inhibits PD-L1 expression by targeting STAT3 and remodels the immune system in tumor-bearing mice.
Insights
Sunitinib, a VEGFR-TKI, inhibits osteosarcoma progression by targeting STAT3 to reduce PD-L1 expression. Combination therapy with immune checkpoint inhibitors effectively controls tumor growth and improves survival in mice.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Osteosarcoma remains a significant challenge, necessitating novel therapeutic strategies.
- Combination therapy targeting both tumor growth and immune evasion is crucial for improved outcomes.
Purpose of the Study:
- To investigate the synergistic effects of VEGFR-TKI (Sunitinib) and immune checkpoint inhibitors in osteosarcoma.
- To elucidate the underlying mechanisms of Sunitinib's action on PD-L1 and STAT3 in osteosarcoma.
Main Methods:
- Western blot analysis for PD-L1 and STAT3 expression.
- Cellular assays (CCK-8, Transwell) for proliferation, migration, and invasion.
- In vivo studies in tumor-bearing mice assessing lung metastases, tumor growth, survival, and immune cell populations.
Main Results:
- Sunitinib inhibited STAT3 activation, leading to reduced PD-L1 expression and suppressed osteosarcoma cell migration and invasion.
- Combination therapy significantly decreased lung metastases and tumor growth, enhanced survival, and reversed the tumor immune microenvironment.
Conclusions:
- Sunitinib targets STAT3 to inhibit PD-L1 expression, offering a potential therapeutic avenue for osteosarcoma.
- Combined VEGFR-TKI and immune checkpoint inhibitor therapy demonstrates potent anti-tumor activity and immune modulation in osteosarcoma models.
