RIOK2 Inhibitor NSC139021 Exerts Anti-Tumor Effects on Glioblastoma via Inducing Skp2-Mediated Cell Cycle Arrest and Apoptosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Cell Lines and Culture Conditions
2.3. Proliferation Assays
2.4. Transfection and siRNAs
2.5. Flow Cytometry Analysis of Cell Cycle and Apoptosis
2.6. Total RNA Isolation and Real-Time PCR
- β-actin: 5′-GCAAAGACCTGTACGCCAAC-3′ (forward)
- and 5′-GATCTTCATTGTGCTGGGTGC-3′ (reverse);
- Skp2: 5′-AGACTGGATGAGCTGAACCTCTCC-3′ (forward)
- and 5′-GGTGATGGTCTCTGACACATGCG-3′ (reverse);
- p27: 5′-ACTGAGGCGGAGACGAAGGTG-3′ (forward)
- and 5′-CGCTGTTTGTCTTGGAGGAGGATC-3′ (reverse);
- RIOK2: 5′-TCCAGGGCTATCGGTTGACAAATG-3′ (forward)
- and 5′-TTGCCAACACCCATCTGGTTTCC-3′ (reverse).
2.7. Western Blot Analysis
2.8. Mouse Tumor Model and Treatment
2.9. Quantification and Statistical Analysis
3. Results
3.1. NSC139021 Inhibits Glioblastoma Cell Proliferation through a RIOK2-Independent Mechanism
3.2. NSC139021 Induces Cell Cycle Arrest in G0/G1 Phase
3.3. NSC139021 Arrests Cell Cycle by Regulating the Skp2-p27/p21-CDK2-Rb Signaling Pathway
3.4. NSC139021 Activates p53 Signaling Pathway and Triggers Apoptosis of Glioblastoma Cells
3.5. NSC139021 Suppresses the Proliferation of Glioblastoma In Vivo
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Yu, M.; Hu, X.; Yan, J.; Wang, Y.; Lu, F.; Chang, J. RIOK2 Inhibitor NSC139021 Exerts Anti-Tumor Effects on Glioblastoma via Inducing Skp2-Mediated Cell Cycle Arrest and Apoptosis. Biomedicines 2021, 9, 1244. https://doi.org/10.3390/biomedicines9091244
Yu M, Hu X, Yan J, Wang Y, Lu F, Chang J. RIOK2 Inhibitor NSC139021 Exerts Anti-Tumor Effects on Glioblastoma via Inducing Skp2-Mediated Cell Cycle Arrest and Apoptosis. Biomedicines. 2021; 9(9):1244. https://doi.org/10.3390/biomedicines9091244
Chicago/Turabian StyleYu, Min, Xiaoyan Hu, Jingyu Yan, Ying Wang, Fei Lu, and Junlei Chang. 2021. "RIOK2 Inhibitor NSC139021 Exerts Anti-Tumor Effects on Glioblastoma via Inducing Skp2-Mediated Cell Cycle Arrest and Apoptosis" Biomedicines 9, no. 9: 1244. https://doi.org/10.3390/biomedicines9091244