Oncolytic Coxsackievirus B3 Strain PD-H Is Effective Against a Broad Spectrum of Pancreatic Cancer Cell Lines and Induces a Growth Delay in Pancreatic KPC Cell Tumors In Vivo
Abstract
1. Introduction
2. Results
2.1. PD-H Exhibits Higher Lytic Activity and Stronger Replication in Pancreatic Cancer Cell Lines Compared to H3N-375/1TS and CVA21
2.2. Viral Receptors of PD-H, H3N-375/1TS and CVA21 Are Highly Variably Expressed in Pancreatic Cancer Cells
2.3. PD-H Induces Apoptosis in All Pancreatic Cancer Cell Lines, While H3N-375/1TS and CVA21 Induce Apoptosis in Only a Subset of Pancreatic Cancer Cell Lines
2.4. PD-H Inhibits Growth of Subcutaneous Pancreatic KPC Tumors in a Syngeneic Mouse Model In Vivo
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. Viruses
4.3. Virus Plaque Assay
4.4. Cell Viability Assay
4.5. Virus Growth Curves
4.6. Quantification of CAR, DAF, ICAM-1, and miR Expression
4.7. Heparin Binding Assay
4.8. Determination of Caspase 3/7 Activities
4.9. Histopathological Analysis
4.10. Syngeneic Subcutaneous KPC Cancer Mouse Model
4.11. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Pancreatic Cancer Cell Line | Cell Death | Viral Replication | Receptor mRNA Expression | Apoptosis Induction | ||||||||||
++++ | >80% lysis | ++++ | up to 108 pfu/ml | ++++ | ~100–1000% to control | PD-H sensitive to heparin | +++ | strong more than 5-fold | ||||||
+++ | >60% lysis | +++ | up to 107 pfu/ml | +++ | ~100% to control | ++ | strong | ++ | middle up to 5-fold | |||||
++ | >40% lysis | ++ | up to 106 pfu/ml | ++ | ~10–100% to control | + | visible | + | low up to 2-fold | |||||
+ | >20% lysis | + | up to 105 pfu/ml | + | ~1–10% to control | - | not sensitive | - | no significant induction | |||||
- | no lysis | - | no replication | - | below 1% to control | |||||||||
PD-H | H3N-375/1TS | CVA21 | PD-H | H3N-375/1TS | CVA21 | CAR | DAF | ICAM-1 | PD-H | H3N-375/1TS | CVA21 | |||
KPC | +++ | ++ | - | ++++ | +++ | - | ++++ | - | - | ++ | + | + | - | |
Beta-TC-3 | ++++ | ++++ | - | ++++ | ++++ | - | ++++ | - | - | ++ | + | + | - | |
AsPC-1 | ++++ | ++++ | - | ++++ | ++++ | ++ | +++ | +++ | - | - | +++ | +++ | + | |
MIA Paca-2 | + | - | - | ++++ | +++ | - | + | - | - | ++ | ++ | - | - | |
Capan-1 | ++++ | - | - | ++++ | +++ | ++ | +++ | ++ | +++ | + | ++ | - | ++ | |
Capan-2 | + | - | ++ | +++ | ++ | ++ | ++ | + | ++ | + | + | - | +++ | |
BxPC-3 | - | - | - | +++ | - | + | +++ | ++ | +++ | + | + | - | + |
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Geisler, A.; Dieringer, B.; Elsner, L.; Klopfleisch, R.; Kurreck, J.; Fechner, H. Oncolytic Coxsackievirus B3 Strain PD-H Is Effective Against a Broad Spectrum of Pancreatic Cancer Cell Lines and Induces a Growth Delay in Pancreatic KPC Cell Tumors In Vivo. Int. J. Mol. Sci. 2024, 25, 11224. https://doi.org/10.3390/ijms252011224
Geisler A, Dieringer B, Elsner L, Klopfleisch R, Kurreck J, Fechner H. Oncolytic Coxsackievirus B3 Strain PD-H Is Effective Against a Broad Spectrum of Pancreatic Cancer Cell Lines and Induces a Growth Delay in Pancreatic KPC Cell Tumors In Vivo. International Journal of Molecular Sciences. 2024; 25(20):11224. https://doi.org/10.3390/ijms252011224
Chicago/Turabian StyleGeisler, Anja, Babette Dieringer, Leslie Elsner, Robert Klopfleisch, Jens Kurreck, and Henry Fechner. 2024. "Oncolytic Coxsackievirus B3 Strain PD-H Is Effective Against a Broad Spectrum of Pancreatic Cancer Cell Lines and Induces a Growth Delay in Pancreatic KPC Cell Tumors In Vivo" International Journal of Molecular Sciences 25, no. 20: 11224. https://doi.org/10.3390/ijms252011224
APA StyleGeisler, A., Dieringer, B., Elsner, L., Klopfleisch, R., Kurreck, J., & Fechner, H. (2024). Oncolytic Coxsackievirus B3 Strain PD-H Is Effective Against a Broad Spectrum of Pancreatic Cancer Cell Lines and Induces a Growth Delay in Pancreatic KPC Cell Tumors In Vivo. International Journal of Molecular Sciences, 25(20), 11224. https://doi.org/10.3390/ijms252011224