FOLFOXIRI Resistance Induction and Characterization in Human Colorectal Cancer Cells
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cells and Cell Culture Conditions
2.2. Heterotypic 3D Co-Cultures
2.3. FOLFOXIRI Resistance Induction
2.4. Drugs
2.5. Drug-Doses Conversion
2.6. Cell metabolic Activity Assay
2.7. Immunofluorescence Staining
2.8. mRNA Transcriptome and Analysis
2.9. Statistical Analysis
3. Results
3.1. Establishment of Acquired Resistance to FOLFOXIRI in Human CRC Cell Lines
3.2. Morphological Features in CRC Cells upon FOLFOXIRI Resistance Induction
3.3. Alterations in Gene Expression and Biological Function upon FX Resistance Induction
3.4. Optimized Combination of Tyrosine Kinase Inhibitors Overcomes FX-Resistance in CRC Cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cell Line | Patient | Cancer Stage/Type | Genomic (In)stability | Mutations/Deregulations | FOLFOXIRI Exposure [Weeks] |
---|---|---|---|---|---|
LS174T | Female | 2 (primary) | MSI | KRAS, PIK3CA, BRAF | 60 |
SW620 | Male | 3 (metastatic) | MSS; CIN | APC, KRAS, TP53 | 34 |
DLD1 | Male | 3 (metastatic) | MSI, CIMP | APC, KRAS, PIK3CA, TP53 | 36 |
HCT116 | Male | 1 (primary) | MSI, CIMP | KRAS, PIK3CA | 62 |
Drug [µM] | CUD | FXDLD1 | FXHCT116 | FXSW620 | FXLS174T |
---|---|---|---|---|---|
FA | 0.5 | 0.5 | 0.5 | 0.25 | 0.5 |
5-FU | 10 | 2 | 2 | 6 | 6 |
SN38 | 0.1 | 0.02 | 0.003 | 0.004 | 0.004 |
OX | 0.6 | 0.5 | 0.2 | 0.3 | 0.2 |
Efficacy [% CTRL] ± SD | 48 4.9 | 35 0.7 | 37 8.6 | 45 2.2 |
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Ramzy, G.M.; Boschung, L.; Koessler, T.; Delucinge-Vivier, C.; Docquier, M.; McKee, T.A.; Rubbia-Brandt, L.; Nowak-Sliwinska, P. FOLFOXIRI Resistance Induction and Characterization in Human Colorectal Cancer Cells. Cancers 2022, 14, 4812. https://doi.org/10.3390/cancers14194812
Ramzy GM, Boschung L, Koessler T, Delucinge-Vivier C, Docquier M, McKee TA, Rubbia-Brandt L, Nowak-Sliwinska P. FOLFOXIRI Resistance Induction and Characterization in Human Colorectal Cancer Cells. Cancers. 2022; 14(19):4812. https://doi.org/10.3390/cancers14194812
Chicago/Turabian StyleRamzy, George M., Laura Boschung, Thibaud Koessler, Céline Delucinge-Vivier, Mylène Docquier, Thomas A. McKee, Laura Rubbia-Brandt, and Patrycja Nowak-Sliwinska. 2022. "FOLFOXIRI Resistance Induction and Characterization in Human Colorectal Cancer Cells" Cancers 14, no. 19: 4812. https://doi.org/10.3390/cancers14194812