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作 者:李可嘉[1] 沈小雁[1] 王宏林[2] 郑捷[1] LI Ke-jia;SHEN Xiao-yan;WANG Hong-lin;ZHENG Jie(Department of Dermatology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Precision Research Center for Refractory Diseases,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 201620,China)
机构地区:[1]上海交通大学医学院附属瑞金医院皮肤科,上海200025 [2]上海交通大学医学院附属第一人民医院疑难疾病精准研究中心,上海201620
出 处:《现代免疫学》2023年第1期22-28,共7页Current Immunology
基 金:国家自然科学基金青年项目(30901293);国家临床重点专科建设项目(2012649)。
摘 要:为探究11-羰基-β-乙酰乳香酸(acetyl-11-keto-β-boswellic acid,AKBA)对皮肤T细胞淋巴瘤(cutaneous T cell lymphoma,CTCL)细胞系HuT 78增殖和凋亡的影响及作用机制,用不同浓度的AKBA处理HuT 78细胞系24、48 h后,应用CCK-8法检测HuT 78细胞的增殖;应用FACS检测肿瘤细胞的凋亡水平;通过Real-time PCR及Western blotting检测凋亡相关基因及蛋白的表达水平。结果显示,AKBA通过抑制HuT 78细胞NF-κB抑制蛋白α(NF-κB inhibitor alpha,IκB-α)的磷酸化抑制NF-κB活化;下调抗凋亡蛋白Bcl-xL、Bcl-2的表达,促进caspase3的活化降解,同时上调Fas的配体FasL的表达,对HuT 78细胞发挥抑制增殖和促进凋亡的作用,可作为免疫治疗的候选药物。This study aims to investigate the anti-tumor effects of acetyl-11-keto-β-boswellic acid(AKBA)on cutaneous T cell lymphoma(CTCL)cell line HuT 78,and to explore the underlying mechanisms.After AKBA treatments of different concentrations for 24 and 48 hours,the cell proliferation of HuT 78 cells was measured by CCK-8 assay and the apoptosis induced by AKBA was detected by FACS using AnnexinⅤ/PI staining.The apoptosis-related genes and proteins levels were analyzed by Real-time PCR and Western blotting,respectively.The results showed that AKBA inhibited the proliferation of HuT 78 cells and induced apoptosis through down-regulating NF-κB pathway via inhibiting phosphorylation of NF-κB inhibitor alpha(IκB-α).In the meantime,AKBA down-regulated the anti-apoptosis proteins Bcl-xL and Bcl-2,induced degradation of caspase3 and up-regulated the expression of FasL.In summary,AKBA is a candidate compound for the treatment of CTCL.
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