Tegaserod Maleate Suppresses the Growth of Gastric Cancer In Vivo and In Vitro by Targeting MEK1/2
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Reagents and Antibodies
2.2. Cell Culture
2.3. Cell Proliferation Assay
2.4. Anchorage-Independent Cell Growth Assay
2.5. Anchorage-Dependent Cell Growth Assay
2.6. Western Blotting
2.7. Pull-Down Assay
2.8. In Vitro Kinase Assay
2.9. Cellular Thermal Shift Assay (CETSA)
2.10. Computer Docking Model
2.11. CRISPR/Cas9 Knockout Cell Lines
2.12. PDX Model
2.13. Immunohistochemistry (IHC) Analysis
2.14. Statistical Analysis
3. Results
3.1. Tegaserod Maleate Inhibits GC Cell Proliferation
3.2. Tegaserod Maleate Binds to MEK1 and MEK2
3.3. Tegaserod Maleate Inhibits the MEK1/2-ERK1/2 Signaling Pathway in GC
3.4. Tegaserod Maleate Inhibits Gastric Cancer Cell Growth by Depending on MEK1/2
3.5. Tegaserod Maleate Inhibits the Growth of GC PDX Models
3.6. Tegaserod Maleate Has the Same Inhibitory Effect Compared with MEK1/2 Inhibitor Trametinib
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene Name | Primer Sequences 5′-3′ |
---|---|
sgMEK1#2 | F:CGTTAACTGCAGAGCCGTCG |
R:CGACGGCTCTGCAGTTAACGC | |
sgMEK1#4 | F:GCAGCAGCGAAAGCGCCTTG |
R:CAAGGCGCTTTCGCTGCTGC | |
sgMEK2#4 | F:GACGGCGAGTTGCATTCGTGCAGG |
R:CCTGCACGAATGCAACTCGCCGT | |
sgMEK2#5 | F:GCACACATTACTCGGTGCAGTCGG |
R:CCGACTGCACCGAGTAATGTGTG |
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Wang, Z.; Chen, Y.; Li, X.; Zhang, Y.; Zhao, X.; Zhou, H.; Lu, X.; Zhao, L.; Yuan, Q.; Shi, Y.; et al. Tegaserod Maleate Suppresses the Growth of Gastric Cancer In Vivo and In Vitro by Targeting MEK1/2. Cancers 2022, 14, 3592. https://doi.org/10.3390/cancers14153592
Wang Z, Chen Y, Li X, Zhang Y, Zhao X, Zhou H, Lu X, Zhao L, Yuan Q, Shi Y, et al. Tegaserod Maleate Suppresses the Growth of Gastric Cancer In Vivo and In Vitro by Targeting MEK1/2. Cancers. 2022; 14(15):3592. https://doi.org/10.3390/cancers14153592
Chicago/Turabian StyleWang, Zitong, Yingying Chen, Xiaoyu Li, Yuhan Zhang, Xiaokun Zhao, Hao Zhou, Xuebo Lu, Lili Zhao, Qiang Yuan, Yunshu Shi, and et al. 2022. "Tegaserod Maleate Suppresses the Growth of Gastric Cancer In Vivo and In Vitro by Targeting MEK1/2" Cancers 14, no. 15: 3592. https://doi.org/10.3390/cancers14153592