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Sunitinib inhibits PD-L1 expression in osteosarcoma by targeting STAT3 and remodels the immune system in tumor-bearing mice.
- Source :
-
Future oncology (London, England) [Future Oncol] 2020 Aug; Vol. 16 (24), pp. 1815-1824. Date of Electronic Publication: 2020 Jun 08. - Publication Year :
- 2020
-
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.
- Subjects :
- Animals
B7-H1 Antigen metabolism
Biomarkers
Bone Neoplasms drug therapy
Bone Neoplasms pathology
Cell Line, Tumor
Cell Movement drug effects
Disease Models, Animal
Female
Humans
Immunomodulation drug effects
Immunophenotyping
Mice
Osteosarcoma drug therapy
Osteosarcoma pathology
Sunitinib therapeutic use
Xenograft Model Antitumor Assays
B7-H1 Antigen genetics
Bone Neoplasms etiology
Bone Neoplasms metabolism
Gene Expression Regulation, Neoplastic drug effects
Osteosarcoma etiology
Osteosarcoma metabolism
STAT3 Transcription Factor antagonists & inhibitors
Sunitinib pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1744-8301
- Volume :
- 16
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Future oncology (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 32511016
- Full Text :
- https://doi.org/10.2217/fon-2019-0725