华蟾素逆转白细胞介素-17A引起的弥漫大B细胞淋巴瘤细胞株对利妥昔单抗的耐药  

Cinobufagin reverses the rituximab resistance of DLBCL cell lines induced by IL-17A

作　　者：朱园[1] 刘秀丹[2] 朱志刚[1] 李康保[3] 钟伟杰[1] ZHU Yuan;LIU Xiudan;ZHU Zhigang;LI Kangbao;ZHONG Weijie(Department of Geriatrics,Hematology&Oncology Ward,Guangzhou First People′s Hospital,Guangzhou 510180,China;不详)

机构地区：[1]广州市第一人民医院老年病科血液肿瘤科,广州510180 [2]广州市第一人民医院超声医学科,广州510180 [3]广州市第一人民医院老年病科消化科,广州510180

出　　处：《实用医学杂志》2021年第21期2707-2711,2716,共6页The Journal of Practical Medicine

基　　金：广东省中医药局科研项目(编号:20201252);广东省医学科学技术研究基金项目(编号:A2020188);广州市科技计划项目(编号:202002030175);华南理工大学中央高校基本科研业务费专项资金资助项目(编号:D2200420)。

摘　　要：目的探讨华蟾素能否改善白细胞介素(IL)-17A引起的弥漫大B细胞淋巴瘤(DLBCL)细胞株对利妥昔单抗的耐药,并分析其中可能的机制。方法本研究分别用CCK-8法检测DLBCL细胞株(SU-DHL-2和SU-DHL-4细胞)的增殖,用PI/Annexin V法检测细胞凋亡,用蛋白质印迹法检测cleaved PARP和cleaved caspase-3蛋白的表达,用流式细胞术分析Th17和IL-17^(+)Foxp3^(+)Treg细胞的表达,用ELISA法检测IL-17A、TGF-β和IL-10的表达。结果华蟾素逆转IL-17A引起的DLBCL细胞株对利妥昔单抗的耐药;IL-17A减轻利妥昔单抗诱发的DLBCL细胞株凋亡,而华蟾素逆转IL-17A的这一作用;华蟾素通过升高cleaved PARP和cleaved caspase-3的表达促进DLBCL细胞株的凋亡;华蟾素抑制肿瘤微环境中Th17和IL-17^(+)Foxp3^(+)Treg细胞的分化,降低IL-17A水平。结论华蟾素逆转IL-17A引起的DLBCL细胞株对利妥昔单抗的耐药,华蟾素未来有望成为DLBCL治疗的联合用药之一。Objective To investigate whether cinobufagin can improve the rituximab resistance of diffuse large B-cell lymphoma(DLBCL)cell lines induced by Interleukin(IL)-17 A,and to analyze the possible mechanisms. Methods CCK-8 assay was used to detect the proliferation of DLBCL cell lines(SU-DHL-2 and SU-DHL-4 cells);PI/Annexin vassay was used to detect cell apoptosis;flow cytometry was used to analyze the percentages of Th17 cells and IL-17^(+)Foxp3^(+)Treg cells;Western blot was used to detect the expressions of cleaved PARP and cleaved caspase-3;and ELISA were used to study the expressions of IL-17 A,TGF-β and IL-10. Results Cinobufagin reversed the rituximab resistance of DLBCL cell lines induced by IL-17 A;IL-17 A attenuated the apoptosis of DLBCL cell lines induced by rituximab,while cinobufagin reversed this effect;cinobufagin promoted the apoptosis of DLBCL cell lines by increasing the expressions of cleaved PARP and cleaved caspase-3;cinobufagin inhibited the differentiation of Th17 and IL-17^(+)Foxp3^(+)Treg cells in tumor microenvironment,and then decreased the level of IL-17 A. Conclusion Cinobufagin reverses the rituximab resistance of DLBCL cell lines induced by IL-17 A,which is expected to be one of the combination drugs in the treatment of DLBCL in the future.

关 键 词：华蟾素 白细胞介素-17A 弥漫性大B细胞淋巴瘤 利妥昔单抗耐药 

分 类 号：R551.2[医药卫生—血液循环系统疾病]