Enhanced De Novo Lipid Synthesis Mediated by FASN Induces Chemoresistance in Colorectal Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Public Dataset and Pathway Analysis
2.2. Cell Culture and Reagents
2.3. Gene Silencing and Overexpression with Lentivirus
2.4. Application of Fatty Acid Inhibitors and Palmitate
2.5. Quantitative Real-Time PCR (qRT–PCR) and Western Blot Analyses
2.6. The mRNA-Seq and Analysis
2.7. Cell-Viability, Colony-Formation, and Migration Assays
2.8. Quantification of Triacylglycerol and Neutral Lipids
2.9. Cell-Cycle, ROS, and Apoptosis Assays
2.10. In Vivo Studies
2.11. Statistical Analysis
3. Results
3.1. FASN Expression Was Associated with Worse Prognosis and Poor Oxaliplatin Therapy Response in Colorectal Cancer Patients
3.2. De Novo Fatty Acid Biosynthesis Rescued Colorectal Cancer Cells from Oxaliplatin
3.3. Pharmacological Inhibition of FASN Synergistically Enhanced the Antiproliferative Effect of Oxaliplatin in Human Colorectal Cancer Cells
3.4. The Combination of Orlistat and Oxaliplatin Caused Cell-Cycle Arrest and Facilitated Oxaliplatin-Induced Apoptosis
3.5. Orlistat Promoted Oxaliplatin-Induced Cytotoxicity by Inhibiting Phosphorylation of the MAPK/ERK and PI3K/AKT Pathways
3.6. Decreased Tumor Burden in a Xenograft-Implantation Model of Colorectal Cancer by the Sequential Combination of Orlistat and Oxaliplatin
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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Han, L.; Dai, W.; Luo, W.; Ye, L.; Fang, H.; Mo, S.; Li, Q.; Xu, Y.; Wang, R.; Cai, G. Enhanced De Novo Lipid Synthesis Mediated by FASN Induces Chemoresistance in Colorectal Cancer. Cancers 2023, 15, 562. https://doi.org/10.3390/cancers15030562
Han L, Dai W, Luo W, Ye L, Fang H, Mo S, Li Q, Xu Y, Wang R, Cai G. Enhanced De Novo Lipid Synthesis Mediated by FASN Induces Chemoresistance in Colorectal Cancer. Cancers. 2023; 15(3):562. https://doi.org/10.3390/cancers15030562
Chicago/Turabian StyleHan, Lingyu, Weixing Dai, Wenqin Luo, Li Ye, Hongsheng Fang, Shaobo Mo, Qingguo Li, Ye Xu, Renjie Wang, and Guoxiang Cai. 2023. "Enhanced De Novo Lipid Synthesis Mediated by FASN Induces Chemoresistance in Colorectal Cancer" Cancers 15, no. 3: 562. https://doi.org/10.3390/cancers15030562