Choline Kinase α Inhibitors MN58b and RSM932A Enhances the Antitumor Response to Cisplatin in Lung Tumor Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Primary Cultures of NSCLC Tumors
2.3. Cell Lines and Chemicals
2.4. Cell Proliferation Assays and Combined Index Evaluation
2.5. Flow Cytometric Assay
2.6. Western Blot Analysis
2.7. In Vivo Antitumoral Assays
2.8. Statistical Analysis
3. Results
3.1. Cisplatin-Intrinsic-Resistant NSCLC Tumors Are Sensitive to ChoKα Inhibition
3.2. Synergism of Cisplatin and ChoKα Inhibitors against NSCLC Cells
3.3. ChoKα Inhibitors Potentiate the Antitumoral Efficacy of Cisplatin In Vivo against NSCLC Xenografts, Reducing the Toxicity Associated with Cisplatin Treatment
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Drug | NSCLC Samples | Sensitive (%) | Resistant (%) |
---|---|---|---|
MN58b | 63 | 35 (55.6) | 28 (44.4) |
cDDP | 62 | 31 (50.0) | 31 (50.0) |
Taxol | 62 | 27 (43.5) | 35 (56.5) |
Vinorelbine | 39 | 15 (38.5) | 24 (61.5) |
Gemcitabine | 52 | 18 (34.6) | 34 (65.4) |
Cell Line | IC50 MN58b (μM) | IC50 TCD-717 (μM) | IC50 cDDP (μM) |
---|---|---|---|
H460 | 0.28 ± 0.12 | 1.11 ± 0.4 | 16.60 ± 1.8 |
H460 Stoc | 0.39 ± 0.19 | 1.32 ± 0.43 | 14.95 ± 2.6 |
H460 MN58R | 19.2 ± 2.6 (49) | 9.5 ± 1.19 (7) | 6.60 ± 1.2 (0.4) |
H460 TCD717R | 28.8 ± 10.5 (73) | 10.8 ± 2.26 (8) | 4.98 ± 0.9 (0.3) |
MN58b | Drug | Schedule (Days) | Mean Body Weigth (Day 22) | Tumor Gowth Inhibition (Day 22) | p |
---|---|---|---|---|---|
Control-1 | Vehicle | 1,3,4,5,8,10,11,12,15,17,18,19 | 23.4 | ||
cDDP | cDDP (1 mg/kg) | 1,4,8,11,15,18 | 23 | 33% | 0.3 |
MN58b | MN58b (2 mg/kg) | 1,3,5,8,10,12,15,17,19 | 24.4 | 35% | 0.09 |
Sequential | cDDP (1 mg/kg) | 1,4 | 23.9 | 67% | 0.017 * |
MN58b (2 mg/kg) | 8,10,12,15,17,19 | ||||
Concomitant | cDDP (1 mg/kg) | 1,4,8,11,15,18 | 22.5 | 66% | 0.160 * |
MN58b (2 mg/kg) | 1,3,5,8,10,12,15,17,19 | ||||
Control cDDP | cDDP (4 mg/kg) | 1,3,5,8,10,12,15,17,19 | 17.4 * | 69% | 0.014 * |
TCD-717 | Drug | Schedule (Days) | Mean Body Weigth (Day 22) | Tumor Gowth Inhibition (Day 22) | p |
Control-2 | Vehicle | 1,4,8,11,15,18 | 20.6 | ||
cDDP | cDDP (1 mg/kg) | 1,4,8,11,15,18 | 20.9 | 24% | 0.4 |
TCD-717 | TCD717 (2 mg/kg) | 1,4,8,11,15,18 | 19.9 | 31% | 0.16 |
Sequential | cDDP (1 mg/kg) | 1,4 | 21.2 | 51% | 0.03 * |
TCD717 (2 mg/kg) | 8,11,15,18 | ||||
Concomitant | cDDP (1 mg/kg) | 1,4,8,11,15,18 | 20.1 | 55% | 0.04 * |
TCD717 (2 mg/kg) | 1,4,8,11,15,18 |
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Lacal, J.C.; Perona, R.; de Castro, J.; Cebrián, A. Choline Kinase α Inhibitors MN58b and RSM932A Enhances the Antitumor Response to Cisplatin in Lung Tumor Cells. Pharmaceutics 2022, 14, 1143. https://doi.org/10.3390/pharmaceutics14061143
Lacal JC, Perona R, de Castro J, Cebrián A. Choline Kinase α Inhibitors MN58b and RSM932A Enhances the Antitumor Response to Cisplatin in Lung Tumor Cells. Pharmaceutics. 2022; 14(6):1143. https://doi.org/10.3390/pharmaceutics14061143
Chicago/Turabian StyleLacal, Juan Carlos, Rosario Perona, Javier de Castro, and Arancha Cebrián. 2022. "Choline Kinase α Inhibitors MN58b and RSM932A Enhances the Antitumor Response to Cisplatin in Lung Tumor Cells" Pharmaceutics 14, no. 6: 1143. https://doi.org/10.3390/pharmaceutics14061143
APA StyleLacal, J. C., Perona, R., de Castro, J., & Cebrián, A. (2022). Choline Kinase α Inhibitors MN58b and RSM932A Enhances the Antitumor Response to Cisplatin in Lung Tumor Cells. Pharmaceutics, 14(6), 1143. https://doi.org/10.3390/pharmaceutics14061143