Targeting MDM2 for Neuroblastoma Therapy: In Vitro and In Vivo Anticancer Activity and Mechanism of Action
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. SP141 Inhibits MDM2 in Neuroblastoma Cells, Independent of p53
2.2. SP141 Induces Apoptosis and Cell Cycle Arrest in Neuroblastoma Cells
2.3. SP141 Inhibits the Migration of Neuroblastoma Cells
2.4. SP141 Inhibits Neuroblastoma Xenograft Tumor Growth
3. Discussion
4. Materials and Methods
4.1. Chemicals, Reagents, and Cell Lines
4.2. Assays for the In Vitro Effects of SP141
4.3. Western Blotting
4.4. In Vivo Xenograft Model for Human Cancer
4.5. H&E Staining and Immunohistochemistry
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Neuroblastoma Cell Lines | |||
Cell Lines | p53 Status | Multidrug-Resistant | IC50 (μM) |
NB-1643 | WT | − | 0.36 |
SK-N-SH | WT | − | 0.32 |
NB-EBC1 | WT | − | 0.26 |
CHLA-255 | WT | − | 0.42 |
NGP | WT | − | 0.30 |
NB-1691 | WT | Yes [37] | 0.89 |
LA1-55n | Null | − | 0.62 |
SK-N-AS | MT | − | 0.41 |
SK-N-BE (2) | MT | Yes [38] | 0.29 |
Normal Fibroblast Cell Line | |||
Cell Line | p53 Status | Drug-Resistant | IC50 (μM) |
IMR90 | WT | − | 13.22 [34] |
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Wang, W.; Wang, X.; Rajaei, M.; Youn, J.Y.; Zafar, A.; Deokar, H.; Buolamwini, J.K.; Yang, J.; Foster, J.H.; Zhou, J.; et al. Targeting MDM2 for Neuroblastoma Therapy: In Vitro and In Vivo Anticancer Activity and Mechanism of Action. Cancers 2020, 12, 3651. https://doi.org/10.3390/cancers12123651
Wang W, Wang X, Rajaei M, Youn JY, Zafar A, Deokar H, Buolamwini JK, Yang J, Foster JH, Zhou J, et al. Targeting MDM2 for Neuroblastoma Therapy: In Vitro and In Vivo Anticancer Activity and Mechanism of Action. Cancers. 2020; 12(12):3651. https://doi.org/10.3390/cancers12123651
Chicago/Turabian StyleWang, Wei, Xinjie Wang, Mehrdad Rajaei, Ji Youn Youn, Atif Zafar, Hemantkumar Deokar, John K. Buolamwini, Jianhua Yang, Jennifer H. Foster, Jia Zhou, and et al. 2020. "Targeting MDM2 for Neuroblastoma Therapy: In Vitro and In Vivo Anticancer Activity and Mechanism of Action" Cancers 12, no. 12: 3651. https://doi.org/10.3390/cancers12123651