Table 1.
Effects of WT-GSK-3β, KD-GSK-3β, and pLXSN empty vector on sensitivity of MIA-PaCa-2 pancreatic cancer cells to chemotherapeutic drugs, signal transduction inhibitors, and nutraceuticals. The concentrations presented in the Table 1 represent the inhibitory concentration 50 (IC50) values (determined as previously described [37,49] for tested substances).
| Drug/Agent↓ | +pLXSN | +WT-GSK-3β | Fold Change WT vs. LXSN |
+pLXSN | +KD-GSK-3β | Fold Change KD vs. LXSN |
+WT- GSK-3β |
+KD-GSK-3β | Fold Change WT vs. KD |
|---|---|---|---|---|---|---|---|---|---|
| 5FU (nucleoside analogue) |
6 µM | 12 µM | 2×↑ | 6 µM | 3 µM | 2×↓ | 12 µM | 3 µM | 4×↑ |
| Gemcitabine (nucleoside analogue) |
3.5 nM | 5 nM | 1.4×↑ | 3.5 nM | 2 nM | 1.8×↓ | 5 nM | 2 nM | 2.5×↑ |
| Paclitaxel (microtubule binder) |
1.2 nM | 2.1 nM | 1.8×↑ | 1.2 nM | 1 nM | 1.3×↓ | 2.1 nM | 1 nM | 2.1×↑ |
| Docetaxel (microtubule binder) |
0.15 nM | 0.6 nM | 4×↑ | 0.15 nM | 0.08 nM | 1.9×↓ | 0.6 nM | 0.08 nM | 7.5×↑ |
| Cisplatin (DNA synthesis inh.) |
110 µM | 200 µM | 1.8×↑ | 110 µM | 65 µM | 1.7×↓ | 200 µM | 65 µM | 3×↑ |
| Oxaliplatin (DNA synthesis inh.) |
0.4 µM | 1.1 µM | 2.8×↑ | 0.4 µM | 0.03 µM | 13.3×↓ | 1.1 µM | 0.03 µM | 36.7×↑ |
| Irinotecan (topoisomerase inh.) |
3 µM | 4 µM | 1.3×↑ | 3 µM | 2 µM | 1.5×↓ | 4 µM | 2 µM | 2×↑ |
| Doxorubicin (topoisomerase inh.) |
35 nM | 55 nM | 1.5×↑ | 35 nM | 6 nM | 5.8×↓ | 55 nM | 6 nM | 9.1×↑ |
| Daunorubicin (topoisomerase inh.) |
300 nM | 800 nM | 2.7×↑ | 300 nM | 150 nM | 2×↓ | 800 nM | 150 nM | 5.3×↑ |
| Mitoxantrone (topoisomerase inh.) |
18 nM | 35 nM | 1.9×↑ | 18 nM | 6.5 nM | 2.8×↓ | 35 nM | 6.5 nM | 5.4×↑ |
| Etoposide (topoisomerase inh.) |
800 nM | 1 µM | 1.3×↑ | 800 nM | 550 nM | 1.5×↓ | 1 µM | 550 nM | 1.8×↑ |
| SB415286 (GSK-3α and β inh.) |
120 nM | 300 nM | 2.5×↑ | 120 nM | 15 nM | 8×↓ | 300 nM | 15 nM | 20×↑ |
| Tideglusib (GSK-3β inh.) |
200 nM | 5 µM | 25×↑ | 200 nM | 70 nM | 2.9×↓ | 5 µM | 70 nM | 71.4×↑ |
| BIO (GSK-3α and β inh.) |
300 nM | 800 nM | 2.7×↑ | 300 nM | 150 nM | 2×↓ | 800 nM | 150 nM | 5.3×↑ |
| CHIR99021 (GSK-3α and β inh.) |
350 nM | 650 nM | 1.9×↑ | 350 nM | 170 nM | 2.1×↓ | 650 nM | 170 nM | 3.8×↑ |
| ARRY-543 (EGFR/HER2 inh.) |
400 nM | 2 µM | 5×↑ | 400 nM | 40 nM | 10×↓ | 2 µM | 40 nM | 50×↑ |
| ARS-1620 (KRas inh.) | 5 nM | 30 nM | 6×↑ | 5 nM | 3 nM | 1.7×↓ | 30 nM | 3 nM | 10×↑ |
| PD0325901 (MEK1 inh.) | 125 nM | 280 nM | 2.3×↑ | 125 nM | 35 nM | 3.6×↓ | 280 nM | 35 nM | 8×↑ |
| Rapamycin (mTORC1 blocker) |
0.6 nM | 2 nM | 3.3×↑ | 0.6 nM | 0.28 nM | 2.1×↓ | 2 nM | 0.28 nM | 7.1×↑ |
| ABT-737 (BCL2/BCLXL inh.) |
350 nM | 7 nM | 50×↓ | 350 nM | 350 nM | 1 × | 7 nM | 350 nM | 50×↓ |
| Metformin (Activation of AMPK) |
7 µM | 9 µM | 1.3×↑ | 7 µM | 6 µM | 1.2×↓ | 9µM | 6 µM | 1.7×↓ |
| Berberine (multiple targets, mTORC1, NF-κB, AMPK) | 1.2 µM | 2 µM | 1.7×↑ | 1.2 µM | 600 nM | 2×↓ | 2 µM | 600 nM | 3.3×↑ |
| Chloroquine (autophagy inh. apoptosis inducer) | 0.9 µM | 20 µM | 22×↑ | 0.9 µM | 0.9 µM | 1× | 20 µM | 0.9 µM | 22×↑ |
| OTX008 (Galectin-1 inh.) | 1.1 µM | 1.3 µM | 1.2×↑ | 1.1 µM | 19 nM | 57.9×↓ | 1.3 µM | 19 nM | 68×↑ |
| Tiplaxtinin (Serpine-1 inh.) | 20 nM | 200 nM | 10×↑ | 20 nM | 20 nM | 1× | 200 nM | 10 nM | 20×↑ |
| Vismodegib (Hh inh.) | 5 µM | 8 µM | 1.8×↑ | 5 µM | 5 µM | 1× | 8 µM | 5 µM | 1.8×↑ |
| Gilteritinib (AXL, ALK, FLT3 inh.) |
550 nM | 700 nM | 1.3×↑ | 550 nM | 400 nM | 1.4×↓ | 700 nM | 400 nM | 1.8×↑ |
| Isoliquiritin (multiple targets) |
600 nM | 3 µM | 5×↑ | 600 nM | 28 nM | 21.4×↓ | 3 µM | 28 nM | 107×↑ |