Abstract:

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.

Key words:

cinobufagin, interleukin?17A, diffuse large B cell lymphoma, rituximab resistance