Apigenin Increases SHIP-1 Expression, Promotes Tumoricidal Macrophages and Anti-Tumor Immune Responses in Murine Pancreatic Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. API Reduces Tumor Burden in an Orthotopic Mouse Model of PC (OPC)
2.2. API Suppresses Inflammation, Induces SHIP-1 Expression, and Reduces MDSC Expansion in OPC Mice
2.3. API Increases M1 TAM in the TME of OPC Mice
2.4. API Increases M1 TAM in Heterotopic KC-PC Mice
2.5. M1 TAM are Reduced in Heterotopic PC SHIPKO Mice
2.6. API Induces SHIP-1 Expression and Skews TAM to an M1 Phenotype in the TME of OPC Mice
2.7. API Improves Anti-Tumor Immune Responses in the TME of OPC Mice
3. Discussion
4. Materials and Methods
4.1. Pancreatic Cancer Cell Lines
4.2. Bioflavonoid
4.3. Pancreatic Cancer Murine Models
4.4. Ultrasound Imaging
4.5. Flow Cytometry
4.6. T Cell Activation Assay
4.7. Western Blot
4.8. Quantitative PCR (qPCR)
4.9. Cytometric Bead Array
4.10. Immunohistochemistry Staining
4.11. Indirect Immunofluorescence
4.12. Hematoxylin and Eosin Staining
4.13. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
API | Apigenin |
Bcl-2 | B-cell lymphoma 2 |
CK2 | Casein kinase II |
DAPI | 4′,6-diamidino-2-phenylindole |
DMSO | Dimethyl sulfoxide |
GAPDH | Glyceraldehyde 3-phosphate dehydrogenase |
GM-CSF | Granulocyte macrophage-colony stimulating factor |
HPC | Heterotopic pancreatic cancer |
Inf-MoDC | Inflammatory monocyte-derived dendritic cell |
MCP-1 | Monocyte chemoattractant protein-1 |
MDSC | Myeloid-derived suppressor cells |
OPC | Orthotopic pancreatic cancer |
PI3K | Phosphatidylinositol 3-kinase |
RIPA | Radioimmunoprecipitation assay |
SHIP-1 | Src homology 2 (SH2) domain-containing inositol 5′-phosphatase-1 |
TAM | Tumor-associated macrophages |
TDF | Tumor-derived factors |
TIL | Tumor infiltrating lymphocytes |
TME | Tumor microenvironment |
Tregs | Regulatory T cells |
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Villalobos-Ayala, K.; Ortiz Rivera, I.; Alvarez, C.; Husain, K.; DeLoach, D.; Krystal, G.; Hibbs, M.L.; Jiang, K.; Ghansah, T. Apigenin Increases SHIP-1 Expression, Promotes Tumoricidal Macrophages and Anti-Tumor Immune Responses in Murine Pancreatic Cancer. Cancers 2020, 12, 3631. https://doi.org/10.3390/cancers12123631
Villalobos-Ayala K, Ortiz Rivera I, Alvarez C, Husain K, DeLoach D, Krystal G, Hibbs ML, Jiang K, Ghansah T. Apigenin Increases SHIP-1 Expression, Promotes Tumoricidal Macrophages and Anti-Tumor Immune Responses in Murine Pancreatic Cancer. Cancers. 2020; 12(12):3631. https://doi.org/10.3390/cancers12123631
Chicago/Turabian StyleVillalobos-Ayala, Krystal, Ivannie Ortiz Rivera, Ciara Alvarez, Kazim Husain, DeVon DeLoach, Gerald Krystal, Margaret L. Hibbs, Kun Jiang, and Tomar Ghansah. 2020. "Apigenin Increases SHIP-1 Expression, Promotes Tumoricidal Macrophages and Anti-Tumor Immune Responses in Murine Pancreatic Cancer" Cancers 12, no. 12: 3631. https://doi.org/10.3390/cancers12123631
APA StyleVillalobos-Ayala, K., Ortiz Rivera, I., Alvarez, C., Husain, K., DeLoach, D., Krystal, G., Hibbs, M. L., Jiang, K., & Ghansah, T. (2020). Apigenin Increases SHIP-1 Expression, Promotes Tumoricidal Macrophages and Anti-Tumor Immune Responses in Murine Pancreatic Cancer. Cancers, 12(12), 3631. https://doi.org/10.3390/cancers12123631