1. Artesunate enhances γδ T-cell-mediated antitumor activity through augmenting γδ T-cell function and reversing immune escape of HepG2 cells.
- Author
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Qian P, Zhang YW, Zhou ZH, Liu JQ, Yue SY, Guo XL, Sun LQ, Lv XT, and Chen JQ
- Subjects
- Artesunate, Carcinoma, Hepatocellular pathology, Hep G2 Cells, Humans, Liver Neoplasms pathology, T-Lymphocytes pathology, Artemisinins pharmacology, Carcinoma, Hepatocellular immunology, Immunity, Cellular drug effects, Liver Neoplasms immunology, Receptors, Antigen, T-Cell, gamma-delta immunology, T-Lymphocytes immunology, Tumor Escape drug effects
- Abstract
Objective: To explore the effect and mechanism of artesunate on γδ T cell-mediated antitumor immune responses against hepatoma carcinoma cells (HepG2) in vitro., Methods: Human γδ T cells or HepG2 were respectively treated with artesunate, subjected to co-culture as appropriate, and the following assays were subsequently conducted: CCK8 to examine cell viability; LDH release assay to detect the killing effect of γδ T cells on HepG2 cells; flow cytometry to examine the expression of perforin (PFP) and granzyme B (GraB) of γδ T cells; ELISA to evaluate the levels of TGF-β1 and IL-10 in the collected supernatant of HepG2 cells pretreated with artesunate; and Western blot analysis to examine Fas, FasL, STAT3, p-STAT3 expression of HepG2 cells induced by artesunate. Results: The results showed that the cytotoxicity effect of γδ T cells pretreated with artesunate on HepG2 cells was augmented via elevating the expression of GraB in γδ T cells. Furthermore, treatment with artesunate reversed the inhibition of HepG2 cells on γδ T cells by reducing the secretion of TGF-β1 in HepG2 cells supernatant and enhanced the antitumor effect of γδ T cells against HepG2 cells through increasing the expression of Fas on HepG2 cells, which may be attributed to the inhibition of STAT3 signaling protein., Conclusion: Artesunate has several mechanisms for augmenting the antitumor immune responses mediated by γδ T cells. These results suggested artesunate may be an efficacious agent in the treatment of hepatocellular carcinoma.
- Published
- 2018
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