Re-Evaluation of Combinational Efficacy and Synergy of the Italian Protocol In Vitro: Are We Truly Optimizing Benefit or Permitting Unwanted Toxicity?
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Lines and Drugs
2.2. Viability Assay
2.3. Combination Treatments
2.4. Real-Time PCR Analysis of Steroidogenic Enzymes
2.5. Statistical Analysis
3. Results
3.1. Synergistic Effect of Adrenocortical Carcinoma Cells after Treatment with Varying Concentrations of Chemotherapeutic Drugs in the Italian Protocol
3.2. Effect of Treatment with Varying Concentrations of Chemotherapeutic Drugs in Italian Protocol on Steroidogenesis Enzymes
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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NCI-H295R | SW13 | ||||
---|---|---|---|---|---|
Mitotane | Cisplatin | CI | Mitotane | Cisplatin | CI |
25 | 25 | 0.49291 | 50 | 25 | 0.49291 |
12.5 | 0.25187 | 12.5 | 0.25187 | ||
6.25 | 0.72284 | 6.25 | 0.72284 | ||
3.125 | 3.95163 | 3.125 | 3.95163 | ||
50 | 25 | 0.22882 | 75 | 25 | 0.22882 |
12.5 | 0.12536 | 12.5 | 0.12536 | ||
6.25 | 0.1907 | 6.25 | 0.1907 | ||
3.125 | 0.22456 | 3.125 | 0.22456 | ||
Mitotane | Doxorubicin | CI | Mitotane | Doxorubicin | CI |
25 | 1.25 | 0.0428 | 50 | 1.25 | 0.46056 |
0.625 | 0.03738 | 0.625 | 14.7115 | ||
0.3125 | 0.04454 | 0.3125 | 13.1713 | ||
0.15625 | 0.04637 | 0.15625 | 12.4012 | ||
50 | 1.25 | 0.02699 | 75 | 1.25 | 0.65588 |
0.625 | 0.03741 | 0.625 | 3.0185 | ||
0.3125 | 0.02337 | 0.3125 | 3.56345 | ||
0.15625 | 0.04418 | 0.15625 | 3.17433 | ||
Mitotane | Etoposide | CI | Mitotane | Etoposide | CI |
25 | 37.5 | 0.01439 | 50 | 37.5 | 0.69421 |
18.75 | 0.01629 | 18.75 | 2.37633 | ||
9.375 | 0.04815 | 9.375 | 6.14957 | ||
4.6875 | 0.68287 | 4.6875 | 8.35123 | ||
50 | 37.5 | 0.0665 | 75 | 37.5 | 0.6226 |
18.75 | 0.02978 | 18.75 | 0.96852 | ||
9.375 | 0.01581 | 9.375 | 1.81114 | ||
4.6875 | 0.2288 | 4.6875 | 1.74636 |
(A) | |||||||
Drug Concentrations (M) | Combination Index (CI) | ||||||
Doxorubicin | Etoposide | SW13 | NCI-H295R | ||||
1.25 | 37.5 | 0.05704 | 0.07368 | ||||
0.625 | 18.75 | 0.04269 | 0.52351 | ||||
0.3125 | 9.375 | 0.07947 | 1.10422 | ||||
0.15625 | 4.6875 | 0.06444 | 0.9597 | ||||
Cisplatin | Etoposide | SW13 | NCI-H295R | ||||
25.0 | 37.5 | 2.14524 | 0.30695 | ||||
12.5 | 18.75 | 4.76774 | 1.38877 | ||||
6.25 | 9.375 | 6.28293 | 36.0221 | ||||
3.125 | 4.6875 | 1.8226 | 11.182 | ||||
Cisplatin | Doxorubicin | SW13 | NCI-H295R | ||||
25.0 | 1.25 | 4.70672 | 0.86499 | ||||
12.5 | 0.625 | 2.41979 | 4.23615 | ||||
6.25 | 0.3125 | 1.26733 | 626.994 | ||||
3.125 | 0.15625 | 0.62515 | 313.497 | ||||
(B) | |||||||
SW13 | |||||||
Mitotane | Doxorubicin | Cisplatin | CI | Mitotane | Doxorubicin | Cisplatin | CI |
50.0 | 1.25 | 25.0 | 0.75264 | 75.0 | 1.25 | 25.0 | 0.89046 |
0.625 | 12.5 | 0.47816 | 0.625 | 12.5 | 0.51558 | ||
0.3125 | 6.25 | 0.31046 | 0.3125 | 6.25 | 0.36737 | ||
0.15625 | 3.125 | 0.21563 | 0.15625 | 3.125 | 0.29093 | ||
Mitotane | Doxorubicin | Etoposide | CI | Mitotane | Doxorubicin | Etoposide | CI |
50.0 | 1.25 | 37.5 | 0.04192 | 75.0 | 1.25 | 37.5 | 0.04498 |
0.625 | 18.75 | 0.03672 | 0.625 | 18.75 | 0.03092 | ||
0.3125 | 9.375 | 0.1072 | 0.3125 | 9.375 | 0.09039 | ||
0.15625 | 4.6875 | 0.10291 | 0.15625 | 4.6875 | 0.09362 | ||
Mitotane | Cisplatin | Etoposide | CI | Mitotane | Cisplatin | Etoposide | CI |
50.0 | 25.0 | 37.5 | 2.00493 | 75.0 | 25.0 | 37.5 | 1.50331 |
12.5 | 18.75 | 2.6954 | 12.5 | 18.75 | 1.36302 | ||
6.25 | 9.375 | 3.86777 | 6.25 | 9.375 | 1.03401 | ||
3.125 | 4.6875 | 11.5887 | 3.125 | 4.6875 | 88.4208 | ||
NCI-H295R | |||||||
Mitotane | Doxorubicin | Cisplatin | CI | Mitotane | Doxorubicin | Cisplatin | CI |
25.0 | 1.25 | 25.0 | 1.71632 | 50.0 | 1.25 | 25.0 | 1.33159 |
0.625 | 12.5 | 11.8672 | 0.625 | 12.5 | 16.9827 | ||
0.3125 | 6.25 | 634.151 | 0.3125 | 6.25 | 6.4654 | ||
0.15625 | 3.125 | 23.7892 | 0.15625 | 3.125 | 3.10297 | ||
Mitotane | Doxorubicin | Etoposide | CI | Mitotane | Doxorubicin | Etoposide | CI |
25.0 | 1.25 | 37.5 | 0.07845 | 50.0 | 1.25 | 37.5 | 0.06546 |
0.625 | 18.75 | 0.24998 | 0.625 | 18.75 | 0.25894 | ||
0.3125 | 9.375 | 0.74028 | 0.3125 | 9.375 | 0.33202 | ||
0.15625 | 4.6875 | 0.73815 | 0.15625 | 4.6875 | 0.50166 | ||
Mitotane | Cisplatin | Etoposide | CI | Mitotane | Cisplatin | Etoposide | CI |
25.0 | 25.0 | 37.5 | 0.34045 | 50.0 | 25.0 | 37.5 | 0.40241 |
12.5 | 18.75 | 2.87857 | 12.5 | 18.75 | 0.054566 | ||
6.25 | 9.375 | 10.9307 | 6.25 | 9.375 | 4.00527 | ||
3.125 | 4.6875 | 14.6393 | 3.125 | 4.6875 | 4.39413 |
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Subramanian, C.; McCallister, R.; Kuszynski, D.; Cohen, M.S. Re-Evaluation of Combinational Efficacy and Synergy of the Italian Protocol In Vitro: Are We Truly Optimizing Benefit or Permitting Unwanted Toxicity? Biomedicines 2021, 9, 1190. https://doi.org/10.3390/biomedicines9091190
Subramanian C, McCallister R, Kuszynski D, Cohen MS. Re-Evaluation of Combinational Efficacy and Synergy of the Italian Protocol In Vitro: Are We Truly Optimizing Benefit or Permitting Unwanted Toxicity? Biomedicines. 2021; 9(9):1190. https://doi.org/10.3390/biomedicines9091190
Chicago/Turabian StyleSubramanian, Chitra, Reid McCallister, Dawn Kuszynski, and Mark S. Cohen. 2021. "Re-Evaluation of Combinational Efficacy and Synergy of the Italian Protocol In Vitro: Are We Truly Optimizing Benefit or Permitting Unwanted Toxicity?" Biomedicines 9, no. 9: 1190. https://doi.org/10.3390/biomedicines9091190