Supplementary Table 1

1. Supplementary Table 1 A. CI simulations display synergism (CI < 1), additive effect (CI = 1), or antagonism (CI > 1) for the entire spectrum of effect levels (Fa) in the combination of NFV and BZ (right panel). CIs for experimental values (left panel) are displayed as actual Fa-CI plots in Figure 1B. B. CIs for experimental values are displayed as actual Fa-CI plots in Figure 1D.

2. Supplementary Figure 1 * * RPMI8226 RPMI8226 + + - - - - - - DMSO - - + + - - + + NFV - - - - + + + + Bortezomib - + - + - + - + Z-VAD PARP - Z-VAD Cleaved PARP + Z-VAD Percent sub-G1 DNA Percent cell death - Z-VAD + Z-VAD DMSO NFV Bortezomib NFV+Bortezomib DMSO NFV Bortezomib NFV+Bortezomib

3. Supplementary Figure 2 0.5 h 8 h 24 h + - - - + - - - + - - - DMSO - + - + - + - + - + - + NFV Bortezomib - - + + - - + + - - + + Bcl-2 Bax Fas DR5 precursor DR5 mature DR4 α-Tubulin Mcl-1 Actin H157

4. Supplementary Figure 3 H157 0.5 h 8 h 24 h + - - - + - - - + - - - DMSO - + - + - + - + - + - + NFV Bortezomib - - + + - - + + - - + + P-JNK (54/46 kDa) P-p38 Total p38 P-Akt (S473) P-Akt (T308) Total Akt P-p44/42 Total p44/42 α-Tubulin

5. Supplementary Figure 4 Vehicle Bortezomib NFV C1 C2 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 Bip P-eIF2α Total-eIF2α ATF3 CHOP XBP-1s Caspase 3 Cleaved Caspase 3 Cleaved Caspase 3 Cleaved Caspase 3 PARP Cleaved PARP GAPDH A. H157 Xenograft tumor lysates NFV+Bortezomib

6. Vehicle Bortezomib NFV NFV+Bortezomib C1 C2 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 Ubiqutin GAPDH B. H157 Xenograft tumor lysates HSP70

7. CHOP ATF3 Expression ratio to vehicle Expression ratio to vehicle V N Bz N+Bz V N Bz N+Bz C. RPMI8226 Xenograft tumor lysates

8. Supplementary Figure 5

9. Supplementary Figure 6