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FTY720 Suppresses Liver Tumor Growth and Metastasis by Reducing Circulating Regulating T Cells and Enhancing the Anti-Tumor Effect of Rapamycin.
- Source :
- OncoTargets & Therapy; May2020, Vol. 13, p4743-4754, 12p
- Publication Year :
- 2020
-
Abstract
- Background: In this study, we aimed to study the effect of FTY720 treatment in reducing circulating Tregs level and then suppressing liver tumor metastasis after hepatectomy and I/R injury in animal models. Furthermore, we also investigated the synergistic anti-tumor effect of FTY720 combined with rapamycin on hepatocellular carcinoma. Methods: The effect of FTY720 on suppressing Tregs mobilization and tumor metastasis after hepatectomy was investigated in an orthotopic liver tumor rat model with hepatectomy and hepatic ischemia/reperfusion (I/R) injury. The synergistic anti-tumor effect of FTY720 combined with rapamycin was further explored both in in vitro functional study and in orthotopic liver tumor mouse model. Results: In rat model, hepatic I/R promoted tumor metastasis and increased circulating Tregs after hepatectomy. The treatment of FTY720 reduced liver tumor metastasis and the number of circulating Tregs. Furthermore, FTY720 enhanced the anti-tumor capacity of rapamycin by inhibiting tumor cell proliferation and migration in vitro and reducing tumor growth in vivo through suppressing hepatic stellate cell activation and tumor angiogenesis. Conclusion: FTY720 suppressed liver tumor growth and metastasis by reducing the population of circulating Tregs and enhancing the anti-tumor effect of rapamycin. It was suggested that FTY720 single or combined with rapamycin might provide novel insight for suppressing tumor growth and metastasis for HCC patients. [ABSTRACT FROM AUTHOR]
- Subjects :
- LIVER cancer
TUMOR growth
METASTASIS
T cells
RAPAMYCIN
FINGOLIMOD
Subjects
Details
- Language :
- English
- ISSN :
- 11786930
- Volume :
- 13
- Database :
- Complementary Index
- Journal :
- OncoTargets & Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 143760443
- Full Text :
- https://doi.org/10.2147/OTT.S234394