| 钟伟杰,李庆山,李康保.人骨髓来源间充质干细胞在肿瘤微环境中上调IL-17A水平激活PI3K/Akt通路促进弥漫大B 细胞淋巴瘤生长和化疗耐药[J].中国肿瘤,2020,29(5):379-390. |
| 人骨髓来源间充质干细胞在肿瘤微环境中上调IL-17A水平激活PI3K/Akt通路促进弥漫大B 细胞淋巴瘤生长和化疗耐药 |
| Human Bone Marrow-derived Mesenchymal Stem Cells Promote Growth and Drug-resistance of Diffuse Large B-cell Lymphoma in Tumor Microenvironment by Up-regulating IL-17A Expression via Activating PI3K/Akt Pathway |
| 中文关键词 修订日期：2019-09-03 |
| DOI：10.11735/j.issn.1004-0242.2020.05.A010 |
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| 中文关键词: 间充质干细胞 白细胞介素-17A PI3K/Akt 弥漫性大B细胞淋巴瘤 |
| 英文关键词:mesenchymal stem cells interleukin-17A PI3K/Akt diffuse large B cell lymphoma |
| 基金项目:广东省自然科学基金项目（2018A0303130167）；广东省医学科学技术研究基金项目（A2018258）；广州市卫生和计划生育科技项目（20181A011011） |
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| 中文摘要: |
| 摘 要：［目的］ 探讨影响弥漫大B细胞淋巴瘤（DLBCL）生长和化疗耐药的机制，并分析其中的信号通路。［方法］ 分别采用CCK-8法检测DLBCL细胞株（SU-DHL-2和SU-DHL-4细胞）的增殖，用qRT-PCR和ELISA法检测白细胞介素（IL）-17A的表达，用流式细胞术分析Th17和Treg细胞的表达，用PI/Annexin V法检测细胞凋亡，用基因芯片分析、生物信息分析和蛋白质印迹法验证IL-17A介导的DLBCL生长的信号通路。［结果］ 人骨髓来源间充质干细胞（hBMSCs）联合外周血单个核细胞（PBMCs）在体外促进DLBCL细胞株的增殖。hBMSCs升高PBMCs中Th17和Treg细胞比例，上调IL-17A和TGF-β水平。hBMSCs显著上调PBMCs中RORγt、Foxp3、IL-17A和TGF-βmRNA的相对表达，增加共培养上清液中IL-17A和TGF-β蛋白的水平。IL-17A通过抑制自发或药物诱导的凋亡促进DLBCL细胞增殖和化疗耐药。外源性IL-17A促进了SU-DHL-4细胞的增殖，降低了自发或利妥昔单抗诱导的SU-DHL-4细胞凋亡，而aIL-17A则消除了这些作用。IL-17A上调细胞周期蛋白D2激活PI3K/Akt信号通路。［结论］ hBMSCs在肿瘤微环境中上调IL-17A水平，激活PI3K/Akt通路，促进DLBCL生长和化疗耐药。 |
| 英文摘要: |
| Abstract：［Purpose］To investigate the effect of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) on growth and drug-resistance of diffuse large B-cell lymphoma (DLBCL) and its mechnism. ［Methods］ DLBCL SU-DHL-2 and SU-DHL-4 cells were treated with hBMSCs and peripheral blood mononuclear cells (PBMCs) in vitro. CCK-8 assay was used to detect the proliferation of SU-DHL-2 and SU-DHL-4 cells；qRT-PCR and ELISA were used to study the expression of IL-17A，flow cytometry was used to analyze the percentages of Th17 cells and Treg cells；microarray analysis，bioinformatics analysis and Western blot were used to analyze the pathways of IL-17A mediated DLBCL growth.［Results］ The hBMSCs promoted the proliferation of DLBCL SU-DHL-2 and SU-DHL-4 cells in vitro. hBMSCs induced PBMCs differentiation into Th17 and Treg cells，and increased IL-17A and TGF-β levels in the co-culture supernatants. The hBMSCs significantly up-regulated the relative expressions of RORγt，Foxp3，IL-17A and TGF-β mRNA in PBMCs，increased the levels of IL-17A and TGF-β proteins in the supernatants. IL-17A promoted the growth and drug-resistance of DLBCL cells by inhibiting spontaneous or drug-induced apoptosis. Exogenous IL-17A promoted SU-DHL-4 cell proliferation and inhibited SU-DHL-4 cell spontaneous or drug-induced apoptosis，whereas IL-17A abolished these effects. IL-17A up-regulated cyclin D2 and activated the PI3K/Akt signaling pathway.［Conclusion］ The hBMSCs promote the growth and drug-resistance of DLBCL by elevating IL-17A level via PI3K/Akt pathway in the tumor microenvironment. |
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