Dual inhibition of MYD88 and Sp1 activity leads to synergistic killing in WM cells, and suppression of NF-κB activity. (A) BCWM.1 cells were transfected with either Scr or MYD88-specific siRNA; 24 hours after transfection, BCWM1 cells were treated with either vehicle or TMP and cultured for an additional 24 hours. Cell proliferation was assessed by thymidine uptake and presented as a percentage of control. (B) BCWM.1 cells were transfected with either Scr or MYD88-specific siRNA; 48 hours after transfection, WM cells were treated with either vehicle or TMP and cultured for an additional 4 hours. TNF-α was added for the last 20 minutes. NF-κB p65 TF binding to its consensus sequence on the plate-bound oligonucleotide was analyzed in nuclear extracts. The results represent means ± SD of triplicate experiments. (C-D) BCWM1 and MWCL1 cells were cultured in the absence or presence of IRAK 1/4 inhibitor peptide 407601 and TMP for 24 hours. Cell growth was assessed by [³H]thymidine uptake assay and presented as a percentage of control cells (untreated cells). Data are mean ± SD (n = 3). CIs and fractions affected were generated with CalcuSyn software for each set of combination. CI <1, CI values = 1, and CI values >1 indicate synergism, additive effect, and antagonism, respectively.