Inhibition of IDH3α Enhanced the Efficacy of Chemoimmunotherapy by Regulating Acidic Tumor Microenvironments
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Bioinformatics Analysis
2.2. Cell Line Culture and Drug Treatment
2.3. Construction of Stable Cell Lines
2.4. CCK8 Assay and EdU Assay
2.5. Colony Formation Assays
2.6. Cell Invasion Assay and Wound Healing Assay
2.7. Flow Cytometry
2.8. RNA-seq
2.9. qPCR
2.10. Western Blotting
2.11. Quantification of Glucose Uptake, L-lactate, NAD+/NADH, and ROS
2.12. Chemosensitivity Assay
2.13. In Vivo Experiments
2.14. HE and Immunohistochemistry Assays
2.15. Immunofluorescence
2.16. Statistical Analysis
3. Results
3.1. Upregulation of IDH3α Is Associated with Poor Patient Survival in UCC and LUAD
3.2. Downregulation of IDH3α Exhibited Tumor-Suppressive Functions in Cancer Cell Lines
3.3. IDH3α Regulates the EMT in UCC
3.4. IDH3α Controls Intracellular Redox Status and Glycolysis Ability
3.5. Downregulation of IDH3α Expression Increased Sensitivity to Cisplatin
3.6. IDH3α Knockdown Inhibited UCC Growth In Vivo and Increased CD8+ T Cell Infiltration Proportion after Cisplatin Treatment
3.7. IDH3α Knockdown Enhanced Chemoimmunotherapy Sensitivity by Activating cGAS–STING Pathway
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Zhang, L.; Song, Y.; Dai, X.; Xu, W.; Li, M.; Zhu, Y. Inhibition of IDH3α Enhanced the Efficacy of Chemoimmunotherapy by Regulating Acidic Tumor Microenvironments. Cancers 2023, 15, 1802. https://doi.org/10.3390/cancers15061802
Zhang L, Song Y, Dai X, Xu W, Li M, Zhu Y. Inhibition of IDH3α Enhanced the Efficacy of Chemoimmunotherapy by Regulating Acidic Tumor Microenvironments. Cancers. 2023; 15(6):1802. https://doi.org/10.3390/cancers15061802
Chicago/Turabian StyleZhang, Lingling, Yang Song, Xiaoyan Dai, Wenwen Xu, Mengxia Li, and Yuxi Zhu. 2023. "Inhibition of IDH3α Enhanced the Efficacy of Chemoimmunotherapy by Regulating Acidic Tumor Microenvironments" Cancers 15, no. 6: 1802. https://doi.org/10.3390/cancers15061802