流式细胞术
祖细胞
细胞凋亡
转铁蛋白受体
体内
细胞生长
CD8型
分子生物学
细胞
免疫学
生物
癌症研究
干细胞
医学
细胞生物学
抗原
生物化学
生物技术
作者
Chengyin Li,Fenglin Zhu,Chong Xu,Ping Xiao,Junsong Wen,Xia Zhang,Bin Wu
标识
DOI:10.1016/j.jep.2019.112035
摘要
Dangguibuxue decoction (DGBX), is a well-known traditional Chinese medicine that contains two types of materials used to treat anemia. In this study, we aimed to explore the effect and mechanism of DGBX on abolishing erythroid progenitor cell (Ter119+CD71+) accumulation induced by melanoma.B16/F10 melanoma cells were used to establish transplanted and metastatic melanoma models. DGBX or normal saline were administered intragastrically daily after the models were established. Tumor sizes and metastatic nodules were observed after tumor cell inoculation. To further test the function of DGBX on erythroid progenitor cell (EPC) accumulation and immunosuppressive abilities, the percentage of EPCs in the blood, and spleen were quantified with flow cytometry. The proportion of CD8+ T cells and related functional mediators, IFN-γ and TNF-α,were also quantified with flow cytometry. To further strengthen our in vivo observations, DGBX serum was prepared from the rats three days after DGBX was administered. Liquid chromatography-mass spectrometry was carried out to control the quality of the experiments. B16/F10 melanomacells were cultured with DGBX serum, and proliferation and apoptosis were observed with the CCK8 assay and AnnexinV/7AAD staining, respectively. EPCs were isolated from B16/F10-bearing mice and cultured under erythroid differentiation conditions. EPCs were treated with DGBX serum, and mature red cell proportions and cell denucleations were tested with flow cytometry and Giemsa staining of the cultured EPCs. Flow cytometry and qPCR were used to analyze the effects of DGBX on the expression of key molecules involved in erythroid development and to explore the mechanism by which DGBX relieves abnormal EPC accumulation.DGBX treatments significantly reduced B16 melanoma tumor sizes and metastatic nodules. Most importantly, our study strongly suggested that DGBX could alleviate anemia, and systematically enhance anti-tumor immune responses by reducing abnormal EPC accumulation. Moreover, DGBX serum treatments had no direct effect on tumor cell proliferation and apoptosis, but could promote EPCs to differentiate into mature red blood cells, in vitro. Mechanistically, at least in part, DGBX relieved abnormal EPC accumulation by altering the "master switch" transcription factors, Pu.1 and Gata-1.DGBX significantly alleviates abnormal tumor-induced EPC accumulation, inhibits B16 melanoma progression, and enhances anti-tumor immune responses.
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