Sorafenib induces autophagy and suppresses activation of human macrophage

Jiunn Chang Lin, Chien Liang Liu, Jie Jen Lee, Tsan Pai Liu, Wen Chin Ko, Yu Chuen Huang, Chih Hsiung Wu, Yu Jen Chen

研究成果: 雜誌貢獻文章同行評審

37 引文 斯高帕斯(Scopus)

摘要

Background Sorafenib, a multi-kinase inhibitor approved for treatment of advanced renal cell carcinoma and other malignancies, has been shown as a modulator for dendritic cells. This study was designed to examine the effects of sorafenib on macrophages, the major ontogeny of innate immunity. Materials and methods Macrophages were derived from sorted CD14+ monocytes of human peripheral blood mononuclear cells. Cell viability and surface antigens were examined by trypan blue analysis. Autophagy was characterized by light microscopy and transmission electron microscopy for morphology, Western blotting for microtubule associated light chain protein 3B (LC-3B) I lipidation, and acridine orange staining for acidic component vacuoles. Soluble factors contained in culture medium and serum were measured by ELISA. Results We found that sorafenib inhibited the viability of macrophages accompanied by morphological changes characteristic of autophagy. This autophagy-inducing effect was validated by LC3B-I lipidation and autophagosome accumulation. The surface antigen expression and the function of activated macrophages were inhibited by sorafenib, including the expression of co-stimulatory molecule CD80, phagocytosis, and the production of reactive oxygen species. The secretion of IL-10, but not IL-6, TNF-α nor TGF-β, was reduced by sorafenib. Conclusion Sorafenib, in addition to being a cancer targeted therapeutic agent, can induce autophagy and modulate the function of human macrophages.

原文英語
頁(從 - 到)333-339
頁數7
期刊International Immunopharmacology
15
發行號2
DOIs
出版狀態已發佈 - 二月 2013

ASJC Scopus subject areas

  • 免疫學和過敏
  • 免疫學
  • 藥理

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