Fig. 5

JAK-STAT inhibitors overcome chidamide resistance in NKTL cells. A Combination index values for chidamide and tofacitinib combinatorial treatment in HANK1 and SNK6 cells. Combination index values were calculated with CalcuSyn software as a function of the level of antiproliferative activity. Combination index = 1 denotes additivity, combination index > 1 denotes antagonism, and combination index < 1 denotes synergy. B Proliferation curves in the presence of tofacitinib, chidamide or a combination. C Cell cycle assay for the combined effects of tofacitinib and chidamide in HANK1 and SNK6 cells. D–E Proliferation curves and cell cycle assays for combination treatment with other JAK-STAT inhibitors, ruxolitinib/Stattic and chidamide, in HANK1 cells. F Annexin V/PI staining of HANK1 cells treated with chidamide and tofacitinib/ruxolitinib for 72 h. G Proliferation curves in the presence of tofacitinib/ruxolitinib, romidepsin or a combination in HANK1 cells. H Cell cycle assay for the combination treatment of HANK1 cells with romidepsin and tofacitinib/ruxolitinib for 72 h. I Proliferation curve of NK-S1 cells in the presence of ruxolitinib, chidamide or a combination. J Cell cycle assay for the combination treatment of NK-S1 cells with ruxolitinib and chidamide for 72 h. K Xenograft tumor growth curve of NK-S1 cells in NOD/SCID/IL2rγnull (NSG) mice treated with chidamide at 25 mg/kg, ruxolitinib at 180 mg/kg or both for 12 days. L Body weight of NSG mice bearing NK-S1 tumors treated with chidamide at 25 mg/kg, ruxolitinib at 180 mg/kg or both for 12 days. The results are expressed as the mean ± SD of three independent experiments. *p < 0.05