Pharmacological Inhibition of PP2A Overcomes Nab-Paclitaxel Resistance by Downregulating MCL1 in Esophageal Squamous Cell Carcinoma (ESCC)
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. OXPHOS Is Elevated in Nab-PTX Resistant ESCC Cells
2.2. MCL1 Contributes to Nab-PTX Resistance in ESCC Cells
2.3. PP2A Activity Is Elevated in Nab-PTX Resistant ESCC Cells
2.4. Pharmacological Inhibition of PP2A Inhibits the Growth of Nab-PTX Resistant ESCC Xenografts
2.5. Pharmacological Inhibition of PP2A Resensitizes Nab-PTX Resistant ESCC to Nab-PTX
3. Discussion
4. Materials and Methods
4.1. Cell Lines
4.2. Reagents
4.3. Development of nab-PTX Resistant Cell Lines and Cell Viability Assay
4.4. Proteomics Sample Preparation and LC-MS-Based Proteomics
4.5. Western Blot Analysis
4.6. PPP2CA, and MCL1 Knockdown with siRNA
4.7. Seahorse Analysis (XF Cell Mito Stress Test)
4.8. PP2A Activity Assay
4.9. Cell Apoptosis Assay
4.10. Animal Studies
4.11. Statistical Analysis
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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Song, Q.; Wang, H.; Jiang, D.; Xu, C.; Cui, J.; Zhang, Q.; Wang, H.; Huang, J.; Su, J.; Wu, G.S.; et al. Pharmacological Inhibition of PP2A Overcomes Nab-Paclitaxel Resistance by Downregulating MCL1 in Esophageal Squamous Cell Carcinoma (ESCC). Cancers 2021, 13, 4766. https://doi.org/10.3390/cancers13194766
Song Q, Wang H, Jiang D, Xu C, Cui J, Zhang Q, Wang H, Huang J, Su J, Wu GS, et al. Pharmacological Inhibition of PP2A Overcomes Nab-Paclitaxel Resistance by Downregulating MCL1 in Esophageal Squamous Cell Carcinoma (ESCC). Cancers. 2021; 13(19):4766. https://doi.org/10.3390/cancers13194766
Chicago/Turabian StyleSong, Qi, Herui Wang, Dongxian Jiang, Chen Xu, Jing Cui, Qi Zhang, Haixing Wang, Jie Huang, Jieakesu Su, Gen Sheng Wu, and et al. 2021. "Pharmacological Inhibition of PP2A Overcomes Nab-Paclitaxel Resistance by Downregulating MCL1 in Esophageal Squamous Cell Carcinoma (ESCC)" Cancers 13, no. 19: 4766. https://doi.org/10.3390/cancers13194766