FL118 Enhances Therapeutic Efficacy in Colorectal Cancer by Inhibiting the Homologous Recombination Repair Pathway through Survivin–RAD51 Downregulation
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Compounds and Antibodies
2.2. Cell Culture and SN38-Resistant LOVO Cell Establishment
2.3. Cell Viability Assay and Normal Cell Toxicity
2.4. Western Blot
2.5. Flow Cytometry Analysis
2.6. Comet Assay
2.7. Immunofluorescence and Foci Analysis
2.8. qRT-PCR
2.9. Drug Combination Analysis
2.10. Expression and RNA-Seq Data Analysis
2.11. Transfection
2.12. Xenografts
2.13. Immunohistochemistry
2.14. Statistical Analysis
3. Results
3.1. FL118 Triggered Apoptosis and G2/M Arrest by Suppressing Apoptosis Protein and Cell Cycle Protein
3.2. FL118 Forms DSBs and Elevates Levels of Phosphorylated ATM and Phosphorylated γH2AX
3.3. FL118 Downregulates the Homologous Recombination (HR) Repair Gene RAD51
3.4. FL118-Mediated Survivin Inhibition Downregulated RAD51
3.5. FL118 Overcomes SN38 Resistance by Effectively Blocking the DNA Repair Mechanism
3.6. FL118 Suppresses Tumor Growth in Both LOVO and LOVO SN38R Cell-Derived Xenograft Models
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Kim, J.; Jeong, Y.; Shin, Y.M.; Kim, S.E.; Shin, S.J. FL118 Enhances Therapeutic Efficacy in Colorectal Cancer by Inhibiting the Homologous Recombination Repair Pathway through Survivin–RAD51 Downregulation. Cancers 2024, 16, 3385. https://doi.org/10.3390/cancers16193385
Kim J, Jeong Y, Shin YM, Kim SE, Shin SJ. FL118 Enhances Therapeutic Efficacy in Colorectal Cancer by Inhibiting the Homologous Recombination Repair Pathway through Survivin–RAD51 Downregulation. Cancers. 2024; 16(19):3385. https://doi.org/10.3390/cancers16193385
Chicago/Turabian StyleKim, Jungyoun, Yeyeong Jeong, You Me Shin, Sung Eun Kim, and Sang Joon Shin. 2024. "FL118 Enhances Therapeutic Efficacy in Colorectal Cancer by Inhibiting the Homologous Recombination Repair Pathway through Survivin–RAD51 Downregulation" Cancers 16, no. 19: 3385. https://doi.org/10.3390/cancers16193385
APA StyleKim, J., Jeong, Y., Shin, Y. M., Kim, S. E., & Shin, S. J. (2024). FL118 Enhances Therapeutic Efficacy in Colorectal Cancer by Inhibiting the Homologous Recombination Repair Pathway through Survivin–RAD51 Downregulation. Cancers, 16(19), 3385. https://doi.org/10.3390/cancers16193385