Figure 4.

Molecular effects of nelfinavir in combination with bortezomib on myeloma cells. RPMI8226 myeloma cells were exposed to bortezomib (bor, 20 nℳ) and nelfinavir (nelfi, 20 μℳ) alone or in combination in vitro. Cells treated with tunicamycin (TM, 6 mg/ml) served as a positive control for UPR induction. Western blot was performed to compare the degree of UPR activation and its translation into apoptosis (BiP, PDI, CHOP, cleaved PARP, upper left panel), the cellular translation of proteasome inhibition (p27, p-IκBα, polyubiquitinated protein), the activation of the three major UPR-inducing signals (p-elF2α, cleaved active ATF6, p-IRE1α expression; upper right), as well as the UPR-dependent activation of caspases 4, 8 and 9 (lower left) and the effect of nelfinavir+bortezomib on the mitogen-activated protein kinase pathways (p-ERK, p-JNK, p-p38, p-c-JUN; lower right).