Inhibition of CDK4/CDK6 is the basis for sensitization to cytotoxic killing. MM1.S cells were infected with CDK4, CDK6, or a nontargeting (n-t) shRNA (sh) lentivirus. (A) Immunoblotting and BrdU⁺ uptake at 66 hours after infection. (B) Percentage of live cells was determined at 17 hours of BTZ (4nM) treatment starting at 72 hours after infection, using the n-t shRNA lentivirus-infected cells without treatment as a control. (C) Left: Rb protein expression in MM1.S and U266 cells. Middle: Percentage of S phase and viable U266 cells after culturing with PD for 24 hours relative to input. Right: MT⁻ U266 cells after BTZ treatment (24 hours) in the absence (Cntl) or presence of PD pretreatment (pG1; 0.5μM, 24 hours). (D) Caspase and poly ADP-ribose polymerase cleavage in MM1.S cells after BTZ treatment (12 hours) in pG1 (PD, 24 hours) or left untreated (Cntl), in the presence or absence of HS-5 BMSCs. (E) Q-VD-OPh (20μM) or DMSO was added to MM1.S cells in pG1 or left untreated for 1 hour before BTZ pulsing (120nM). MT⁻ cells were determined at 7 hours from BTZ pulsing. Data are representative of 3 independent experiments.