Fig. 3

DT2216 can synergistically kill TCL PDX cells in combination with ABT199 in vitro.a The viability of DFTL-28776 PDX cells was determined 24 h after doxorubicin (Dox), etoposide (Eto), or vincristine (Vin) treatment. EC₅₀, half maximal effective concentration. The data presented are mean ± SD (n = 2 independent assays, with 3 replicates in each assay). b The viability of DFTL-28776 PDX cells was determined 24 h after ABT263, ABT199, A-1155463, or S63845 treatment. The data presented are mean ± SD (n = 2 independent assays, with 3 replicates in each assay). c Bcl-xL, Bcl-2, Mcl-1, and VHL expressions in MyLa cells, DFTL-28776 PDX cells, and PLT. d DT2216 degraded Bcl-xL in DFTL-28776 PDX cells after treatment with indicated concentrations of DT2216 for 16 h. e VHL ligand (VHL-L) pretreatment blocked the degradation of Bcl-xL induced by DT2216 in DFTL-28776 PDX cells. The PDX cells were pretreated with 10 μM VHL-L for 2 h, and then treated with indicated concentrations of DT2216 for 16 h. f Proteasome inhibition with MG132 blocked the degradation of Bcl-xL induced by DT2216 in DFTL-28776 PDX cells. The PDX cells were pretreated with 1 μM MG-132 for 2 h and then treated with the indicated concentrations of DT2216 for 16 h. g The viability of DFTL-28776 PDX cells was determined 24 h after treatment with DT2216, ABT199, or DT2216 plus ABT199 (DT+199 at a ratio of 1:1). The data presented are mean ± SD (n = 2 independent assays, with 3 replicates in each assay). h The combination index (CI) values of DT+199 group at EC₂₅, EC₅₀, and EC₇₅, values calculated from the data presented in g are presented. i Combination of DT2216 with ABT199 induced apoptosis in PDX cells. Apoptosis was assayed after treatment with 0.1 μM DT2216, 0.1 μM ABT199, or combination of 0.1 μM DT2216 with 0.1 μM ABT199 for 24 h. PI, propidium iodide