Table 3.
Synergistic effects of NSAIDs with canonical anti-cancer drugs at sub-IC50 concentrations in bidimensional HeLa cell cultures—Resistance index.
| HeLa Bidimensional Cultures | 3T3 Bidimensional Cultures | ||||
|---|---|---|---|---|---|
| Drug 1 | Assayed Doses (µM) | Drug 2 | Assayed Doses (µM) | RI Value (Range) | RI Value (Range) |
| Celecoxib | 5–7 | Cisplatin | 1–5 | 13 ± 11 (4.4–28) | 1.4 ± 0.7 (0.5–2.1) |
| 5–7 | Paclitaxel | 11–15 | 4 ± 2 (3.6–6) | 0.8 ± 0.2 (0.6–0.9) | |
| 5–10 | Doxorubicin | 15–20 | 7 ± 6 (3.7–16.5) | 1.3 ± 0.4 (0.9–1.7) | |
| DMC | 10–15 | Cisplatin | 4–5 | 6 ± 4 (3.1–12.6) | 1.2 ± 0.4 (0.7–1.4) |
| 20–25 | Paclitaxel | 20–21 | 7 ± 3.5 (4–11) | 0.5 ± 0.2 (0.3–0.6) | |
| 25 | Doxorubicin | 17 | 3 ± 0.4 (2.9–3.5) | 0.4 ± 0.1 (0.3–0.5) | |
| CasII-gly | 0.5–1 | Cisplatin | 5–10 | 18 ± 23 (5–61) | 0.4 ± 0.1 (0.3–0.5) |
| 0.5–1 | Paclitaxel | 10–20 | 10 ± 11 (3.2–27) | 0.5 ± 0.3 (0.3–0.8) | |
| 0.5–1 | Doxorubicin | 13 | 5 ± 4 (6.6–11) | 0.5 ± 0.1 (0.3–0.65) | |
| MCTS Preventive Protocol | |||||
| Drug 1 | Assayed Doses (nM) | Drug 2 | Assayed Doses (nM) | RI Value (Range) | |
| Celecoxib | 0.4–0.7 | Cisplatin | 10–30 | 3 ± 1 (2.2–5.5) | |
| 0.1–0.9 | Paclitaxel | 10–13 | 3 ± 0.8 (2.3–4.7) | ||
| 0.1–0.5 | Doxorubicin | 40 | 4.5 ± 2 (2.9–7.3) | ||
| DMC | 1–7 | Cisplatin | 30 | 6 ± 2 (3.6–8.3) | |
| 5 | Paclitaxel | 10–13 | 6 ± 3 (3.1–8.7) | ||
| 1 | Doxorubicin | 30–40 | 3 ± 0.4 (2.3–3) | ||
| CasII–gly | 10–15 | Cisplatin | 30 | 4 ± 1 (2–5) | |
| 2–3 | Paclitaxel | 13 | 4 ± 3 (2–8) | ||
| 20–25 | Doxorubicin | 25 | 4 ± 2 (2–7) | ||
| MCTS Curative Protocol | |||||
| Drug | Assayed Doses (µM) | Chemotherapy drugs | assayed doses (µM) | RI Value (Range) | |
| Celecoxib | 2–5 | Cisplatin | 3–5 | 4 ± 2 (2–7.4) | |
| 2 | Paclitaxel | 15–20 | 7 ± 5 (2–15) | ||
| 4 | Doxorubicin | 30–50 | 5 ± 3 (2–8) | ||
| DMC | 10–25 | Cisplatin | 2–5 | 4 ± 2 (2–6.9) | |
| 20 | Paclitaxel | 20–25 | 4 ± 2 (4–6) | ||
| 35 | Doxorubicin | 50 | 3 ± 1 (1.8–4) | ||
| CasII-gly | 11–12 | Cisplatin | 30 | 6 ± 4 (3–11) | |
| 20 | Paclitaxel | 15 | 1 ± 0.1 (0.9–1.3) | ||
| 30 | Doxorubicin | 10 | 3 ± 0.8 (2–4) | ||
The data shown represent the mean ± S.D. of at least three different independent bidimensional (n = 3) or tridimensional (n = 3) cultures. From each tridimensional culture, 10 spheroids were analyzed (total = 30 spheroids). The bold range indicates stronger drug synergy was achieved when combining celecoxib or CasII-gly with cisplatin or paclitaxel.