Study on the molecular mechanisms of sorafenib inhibiting human peripheral blood T cells
10.3760/cma.j.issn.0254-5101.2010.01.017
- VernacularTitle:索拉非尼抑制T淋巴细胞的分子机制研究
- Author:
Yanhong GU
;
Renhua GUO
;
Yongqian SHU
- Publication Type:Journal Article
- Keywords:
Sorafenib;
T cells
- From:
Chinese Journal of Microbiology and Immunology
2010;30(1):66-70
- CountryChina
- Language:Chinese
-
Abstract:
Objective To elucidate the molecular mechanisms of sorafenib inhibitting human pe-ripheral blood T cells. Methods CFSE(5, 6-carboxyfluorescein diacetate succinimidyl ester) proliferation assay and MTS [3-(4, 5-diethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl) -2-( 4-sulfophenyl) -2H-etrazoli-um, inner salt] assay were used to examine the proliferation and the viability of T cells; Annexin V-FITC and PI staining was used to detect apoptosis; Flow cytometry was used to detect the expression of CD25, CD69; Western blot was used to detect the expression of cell cycle proteins; ELISA was used to detect the level of IL-2; Picryl chloride-induced delayed-type hypersensitivity model to be used to for the evaluation of in vivo immunocompetency. Results Sorafenib inhibited proliferation of human peripheral blood T cells in-duced by phytohemagglutinin(PHA) in a dose-dependent manner without inducing their apeptosis. Sorafenib caused human blood T cells arrest in the G_0/G_1 phase of the ceLl cycle. Sorafenib decreased CD25 and CD69 expressions and IL-2 production in human T cells. Sorafenib inhibited picryl chloride-induced delayed-type hypersensitivity in mice. Conclusion Sorafenib could inhibit proliferation and activation of peripheral blood T cells. These finding indicated that long term administration of sorafenib might lead to immunosuppressive effects.
