Activation of ERK and p38 Reduces AZD8055-Mediated Inhibition of Protein Synthesis in Hepatocellular Carcinoma HepG2 Cell Line
Abstract
:1. Introduction
2. Results
2.1. The mTOR Inhibitor AZD8055 Was Selected during the Screening Process as an Anticancer Drug with Inhibitory Effects on Protein Translation
2.2. AZD8055 Inhibits Protein Synthesis and Up-Regulates Phosphorylation of ERK1/2 in Hepatocellular Carcinoma HepG2 Cells
2.3. AZD8055 Up-Regulates Phosphorylation of ERK1/2 and p38 and Independently Down-Regulates Phosphorylation of 4E-BP1
2.4. AZD8055-Mediated ERK1/2 Up-Regulation Was Associated with AZD8055-Mediated Inhibition of Protein Synthesis
2.5. Activation of p38 by AZD8055 Treatment Was Associated with AZD8055-Mediated Inhibition of Protein Synthesis
2.6. AZD8055 Regulates the 4E-BP1 mRNA Pool by Up-Regulating ERK1/2 and p38 Pathways
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. Cell Lines and Cell Culture
4.3. Puromycin Incorporation Assay and Analysis
4.4. Measurement of Cell Viability
4.5. Immunoblot Analysis
4.6. Reverse-Transcription Polymerase Chain Reaction (RT-PCR) and Real-Time Quantitative PCR (qPCR) Primers
4.7. Statistical Analysis
5. Conclusions
- Anticancer drugs that inhibit protein synthesis were selected in MEFs through screening using puromycin incorporation assay.
- AZD8055 inhibits translation in hepatocellular carcinoma HepG2 cell lines.
- AZD8055 inhibits 4E-BP1 phosphorylation and induces ERK1/2 and p38 phosphorylation, which are independent of each other.
- Combined treatment of AZD8055 with refametinib or SB203580 has a synergistic effect on translational inhibition than AZD8055 treatment alone.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Jee, H.-y.; Lee, Y.-G.; Lee, S.; Elvira, R.; Seo, H.-e.; Lee, J.-Y.; Han, J.; Lee, K. Activation of ERK and p38 Reduces AZD8055-Mediated Inhibition of Protein Synthesis in Hepatocellular Carcinoma HepG2 Cell Line. Int. J. Mol. Sci. 2021, 22, 11824. https://doi.org/10.3390/ijms222111824
Jee H-y, Lee Y-G, Lee S, Elvira R, Seo H-e, Lee J-Y, Han J, Lee K. Activation of ERK and p38 Reduces AZD8055-Mediated Inhibition of Protein Synthesis in Hepatocellular Carcinoma HepG2 Cell Line. International Journal of Molecular Sciences. 2021; 22(21):11824. https://doi.org/10.3390/ijms222111824
Chicago/Turabian StyleJee, Ha-yeon, Yoon-Gyeong Lee, Sol Lee, Rosalie Elvira, Hye-eun Seo, Ji-Yeon Lee, Jaeseok Han, and Kyungho Lee. 2021. "Activation of ERK and p38 Reduces AZD8055-Mediated Inhibition of Protein Synthesis in Hepatocellular Carcinoma HepG2 Cell Line" International Journal of Molecular Sciences 22, no. 21: 11824. https://doi.org/10.3390/ijms222111824