Sinomenine Hydrochloride Inhibits the Metastasis of Human Glioblastoma Cells by Suppressing the Expression of Matrix Metalloproteinase-2/-9 and Reversing the Endogenous and Exogenous Epithelial-Mesenchymal Transition
Abstract
:1. Introduction
2. Results
2.1. Sinomenine Hydrochloride (SH) Selectively Kills Human Glioblastoma Cells, But Not Normal Glial Cells, and Induces Human Glioblastoma Cell Cycle Arrest
2.2. SH Inhibits the Migration and Invasion of U87 and SF767 Cells
2.3. SH Decreases MMP-2/-9 Expression by Suppressing NFκB Activation
2.4. SH Impairs the Invasiveness of Human Glioblastoma Cells by Reversing the Endogenous EMT through ER Stress-Mediated Autophagy
2.5. SH Inhibits the EMT and Invasion of Human Glioblastoma Cells in the Inflammatory Microenvironment
2.5.1. Establishment of an Inflammatory Microenvironment System
2.5.2. SH Abolishes THP-1-CM-Stimulated Exogenous EMT and Invasion in U87 and SF767 Cells
2.6. SH Regulates the Levels of Proliferation and Metastasis-Related Proteins in Glioblastoma Tumors In Vivo
3. Discussion
4. Materials and Methods
4.1. Reagents and Antibodies
4.2. Cell Culture and Treatment
4.3. Cell Viability Measurement
4.4. Cell Cycle Analysis
4.5. In Vitro Migration and Invasion Assays
4.6. Quantitative Real-Time PCR
4.7. Co-IP Analysis
4.8. Confocal Microscopy
4.9. Plasmids and siRNA Transfection
4.10. Measurement of Intracellular Ca2+ Concentrations
4.11. ELISA
4.12. Western Blot
4.13. Immunohistochemistry
4.14. Statistical Analysis
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
SH | Sinomenine hydrochloride |
LC3B | Microtubule-associated protein light chain 3B |
3-MA | 3-methyladenine |
MDC | Monodansylcadaverine |
ATG5 | Autophagy-related 5 |
siRNA | Small interfering RNA |
MMP | Matrix metalloproteinase |
ER | Endoplasmic reticulum |
EMT | Epithelial-mesenchymal transition |
CHOP | C/EBP homologous protein |
4-PBA | 4-phenylbutyric acid |
ECM | Extracellular matrix |
UPR | Unfolded protein response |
TNF-α | Tumor necrosis factor-α |
IL-1β | Interleukin-1β |
PERK | Eukaryotic translation initiation factor 2α kinase 3 |
GRP78 | ER intraluminal 78 kDa glucose-regulated protein |
eIF2α | Eukaryotic translation initiation factor 2α |
AVs | Autophagic vacuoles |
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Jiang, Y.; Jiao, Y.; Liu, Y.; Zhang, M.; Wang, Z.; Li, Y.; Li, T.; Zhao, X.; Wang, D. Sinomenine Hydrochloride Inhibits the Metastasis of Human Glioblastoma Cells by Suppressing the Expression of Matrix Metalloproteinase-2/-9 and Reversing the Endogenous and Exogenous Epithelial-Mesenchymal Transition. Int. J. Mol. Sci. 2018, 19, 844. https://doi.org/10.3390/ijms19030844
Jiang Y, Jiao Y, Liu Y, Zhang M, Wang Z, Li Y, Li T, Zhao X, Wang D. Sinomenine Hydrochloride Inhibits the Metastasis of Human Glioblastoma Cells by Suppressing the Expression of Matrix Metalloproteinase-2/-9 and Reversing the Endogenous and Exogenous Epithelial-Mesenchymal Transition. International Journal of Molecular Sciences. 2018; 19(3):844. https://doi.org/10.3390/ijms19030844
Chicago/Turabian StyleJiang, Yumao, Yue Jiao, Yang Liu, Meiyu Zhang, Zhiguo Wang, Yujuan Li, Tao Li, Xiaoliang Zhao, and Danqiao Wang. 2018. "Sinomenine Hydrochloride Inhibits the Metastasis of Human Glioblastoma Cells by Suppressing the Expression of Matrix Metalloproteinase-2/-9 and Reversing the Endogenous and Exogenous Epithelial-Mesenchymal Transition" International Journal of Molecular Sciences 19, no. 3: 844. https://doi.org/10.3390/ijms19030844