IGF2 Mediates Resistance to Isoform-Selective-Inhibitors of the PI3K in HPV Positive Head and Neck Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Tumor Cell Lines
2.2. IC50 and Synergy Assay
2.3. Cell Proliferation Assay
2.4. Cell Cycle
2.5. RNAseq
2.6. Real-Time PCR
2.7. siRNA Transfection
2.8. Western Blotting
2.9. Immunohistochemistry (IHC) and Immunofluorescence (IF)
2.10. Tumor Ex Vivo Analysis (TEVA)
2.11. Establishment of Tumor Xenografts and Studies in Mice
2.12. Antibodies
2.13. Drugs and Reagents
2.14. Statistics
2.15. Study Approval
3. Results
3.1. Generation of BYL719- and GDC0032-Acquired Resistance HNCHPV+ Cell Lines
3.2. FOXO Signaling Pathway Is Activated in isiPI3K-Resistant Cells
3.3. Overexpression of IGF2 Limits the Vulnerability to isiPI3K
3.4. IGF1R Inhibition Synergizes with isiPI3K to Inhibit Tumor Cells
3.5. Dual Treatment with isiPI3K and AEW541 Induced Growth Arrest in PDXHPV+ Ex Vivo
3.6. Dual Treatment with isiPI3K and AEW541 Induced Tumor Growth Arrest in Mice
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Badarni, M.; Prasad, M.; Golden, A.; Bhattacharya, B.; Levin, L.; Yegodayev, K.M.; Dimitstein, O.; Joshua, B.-Z.; Cohen, L.; Khrameeva, E.; et al. IGF2 Mediates Resistance to Isoform-Selective-Inhibitors of the PI3K in HPV Positive Head and Neck Cancer. Cancers 2021, 13, 2250. https://doi.org/10.3390/cancers13092250
Badarni M, Prasad M, Golden A, Bhattacharya B, Levin L, Yegodayev KM, Dimitstein O, Joshua B-Z, Cohen L, Khrameeva E, et al. IGF2 Mediates Resistance to Isoform-Selective-Inhibitors of the PI3K in HPV Positive Head and Neck Cancer. Cancers. 2021; 13(9):2250. https://doi.org/10.3390/cancers13092250
Chicago/Turabian StyleBadarni, Mai, Manu Prasad, Artemiy Golden, Baisali Bhattacharya, Liron Levin, Ksenia M. Yegodayev, Orr Dimitstein, Ben-Zion Joshua, Limor Cohen, Ekaterina Khrameeva, and et al. 2021. "IGF2 Mediates Resistance to Isoform-Selective-Inhibitors of the PI3K in HPV Positive Head and Neck Cancer" Cancers 13, no. 9: 2250. https://doi.org/10.3390/cancers13092250