11-羰基-β-乙酰乳香酸对皮肤T细胞淋巴瘤细胞系HuT 78增殖、凋亡的作用研究

Effects of acetyl-11-keto-β-boswellic acid on proliferation and apoptosis of cutaneous T cell lymphoma cell line Hut 78

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.