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）⁃17A，and to analyze the possible mecha⁃ nisms. 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⁃17A，TGF⁃β and IL⁃10. Results Cinobu⁃ fagin reversed the rituximab resistance of DLBCL cell lines induced by IL⁃17A；IL⁃17A 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-17A. Conclusion Cinobufagin reverses the rituximab resistance of DLBCL cell lines induced by IL-17A，which is expected to be one of the combination drugs in the treatment of DLBCL in the future.