1. Supplementary Figure 1
100 B. 50

2. Supplementary Figure 2 Supplementary Figure 3 Cell Viability, %
RPMI8226
100
100
Cell Viability, % 50
Cell Viability, % 50
Bortezomib, nM
Metformin, µM
100
100
U266
Cell Viability, % 50
Cell Viability, % 50
Bortezomib, nM
100 SP
RPMI8226
U266
Metformin, µM
Colony Formation, % 50
Metformin, µM

3. Supplementary Figure 4 100 RPMI8226 Colony Formation, % 50
Metformin, µM
100
U266

4. Supplementary Figure 5 Supplementary Figure 6 Cell Viability, %
No Addition
Chloroquine
Hydroxychloroquine
Bafilomycin A1
No Drug
Bortezomib 5nM
Metformin 500µM
Bortezomib 5nM + Metformin 500µM
100
100
Cell Viability, %
Cell Viability, % 50 50
Drug Treatment
Bortezomib, nM

5. Supplementary Figure 7

6. PARP Supplementary Figure 8 SP MP SP MP Bortezomib
Metformin
PI3K-p85
PI3K-p110
β- Actin
P -Ser473-AKT
β- Actin
Total AKT
P -AKT/AKT
Bortezomib
Metformin SP MP
Bortezomib
Metformin
PARP
Cleaved PARP
β-Tubulin

7. Supplementary Figure 14 Supplementary Figure 9 Untreated 22 Metformin
BTZ
BTZ + Metformin 22
Mean Body Weight, grams 20 18
Days from Start of Treatment

8. Supplementary Figure 10 Supplementary Figure 14 Untreated 22 Metformin
BTZ
BTZ + Metformin 22
Mean Body Weight, grams 20 18
Days from Start of Treatment

9. Annexin-positive cells (%)
Supplementary Figure 11
Supplementary Figure 12 70
AMPK-WT
AMPK-a1/a2 KO
shRNA
Control
HSPA5 60
120
100 80 60 40 20 50
Cell Viability, % 40
Annexin-positive cells (%) 30 20 10
BTZ (5nM)
Metformin (500µM)
Phenformin (25µM)
Bortezomib, nM

10. Patient #3 Patient #1 Patient #2 Patient #4 Patient #5 Patient #6
Supplementary Figure 13
BTZ
BTZ + Metformin (500µM)
100
Patient #3
Patient #1
100
Patient #2
100
Cell Viability, %
Cell Viability, %
Cell Viability, % 50 50 50
Bortezomib, nM
Bortezomib, nM
Bortezomib, nM
Patient #4
Patient #5
Patient #6
100
100
100
Cell Viability, %
Cell Viability, %
Cell Viability, % 50 50 50
Bortezomib, nM
Bortezomib, nM
Bortezomib, nM

11. Supplementary Figure 14 Untreated 22 Metformin BTZ
BTZ + Metformin 22
Mean Body Weight, grams 20 18
Days from Start of Treatment