Telmisartan Inhibits Cell Proliferation and Tumor Growth of Esophageal Squamous Cell Carcinoma by Inducing S-Phase Arrest In Vitro and In Vivo
Abstract
:1. Introduction
2. Results
2.1. Telmisartan Inhibits the Proliferation Ability of Human ESCC Cells in Vitro
2.2. Telmisartan Induced Cell-Cycle Arrest in S Phase and Regulated Cell-Cycle-Related Proteins
2.3. Telmisartan Does Not Promote KYSE180 Cell Apoptosis
2.4. Telmisartan Affects the p-ErbB3 Level in KYSE180 Cells
2.5. Telmisartan Affected the Thrombospondin-1 (TSP-1) Level in KYSE180 Cells
2.6. Effect of Telmisartan on miRNA Expression
2.7. Telmisartan Inhibits Tumor Growth In Vivo
3. Discussion
4. Material and Methods
4.1. Chemicals
4.2. Cell Lines and Cell Culture
4.3. Cell Proliferation Assay
4.4. Flow Cytometry Analysis of The Cell Cycle and Apoptosis
4.5. Western Blot Analysis
4.6. Antibody Array of Phosphorylated Receptor Tyrosine Kinase (p-RTK) and Angiogenetic Protein Profiles
4.7. Analysis of the miRNA Array
4.8. Xenograft Model Analysis
4.9. Immunohistochemistry
4.10. Statistical Analyses
Author Contributions
Acknowledgments
Conflicts of Interest
References
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miRNA | Fold Change (Treated/Nontreated) | P | Chromosome Site | FDR |
---|---|---|---|---|
Upregulated | ||||
hsa-miR-3064-5p | 10.83 | 0.0010282 | 17q23.3 | 0.011157148 |
hsa-miR-125b-1-3p | 9.11 | 0.001271658 | 11q24.1 | 0.0125323 |
hsa-miR-513b-5p | 6.09 | 0.000497916 | Xq27.3 | 0.006177046 |
hsa-miR-4531 | 5.05 | 5.85714E-05 | 19q13.31 | 0.002005486 |
hsa-miR-6726-5p | 5.03 | 9.25009E-05 | 1p36.33 | 0.002316916 |
hsa-miR-3620-5p | 4.40 | 6.52537E-05 | 1q42.13 | 0.002053966 |
hsa-miR-1587 | 3.94 | 0.000113112 | Xp11.4 | 0.002316916 |
hsa-miR-4465 | 3.48 | 0.002098485 | 6q24.1 | 0.016612376 |
hsa-miR-6861-5p | 3.38 | 3.99841E-05 | 12q24.13 | 0.001651115 |
hsa-miR-6779-5p | 3.27 | 0.000766206 | 17q12 | 0.009109338 |
hsa-miR-4507 | 3.26 | 3.66678E-05 | 14q32.33 | 0.001651115 |
hsa-miR-513a-5p | 3.25 | 0.001965543 | Xq27.3 | 0.016207521 |
hsa-miR-5705 | 3.05 | 0.000161489 | 4q22.1 | 0.002879892 |
hsa-miR-3929 | 3.02 | 0.007579917 | 18q12.2 | 0.037505255 |
hsa-miR-7855-5p | 3.01 | 0.002769579 | 14q23.3 | 0.020416622 |
hsa-miR-3124-5p | 2.94 | 0.030352961 | 1q44 | 0.093125929 |
hsa-miR-4505 | 2.92 | 0.000284337 | 14q24.3 | 0.004425312 |
hsa-miR-4446-3p | 2.89 | 3.70271E-05 | 3q13.2 | 0.001651115 |
hsa-miR-3682-3p | 2.80 | 0.003888419 | 2p16.2 | 0.024658098 |
hsa-miR-575 | 2.63 | 2.92538E-07 | 4q21.22 | 0.000220522 |
hsa-miR-185-3p | 2.62 | 0.008315209 | 22q11.21 | 0.039764351 |
hsa-miR-4741 | 2.54 | 0.00091106 | 18q11.2 | 0.01012815 |
hsa-miR-6132 | 2.49 | 0.002121681 | 7q31.2 | 0.016612376 |
hsa-miR-1181 | 2.48 | 0.000436849 | 19p13.2 | 0.005665799 |
hsa-miR-4773 | 2.42 | 0.012530723 | 2q23.3 | 0.051415576 |
hsa-miR-3187-3p | 2.39 | 0.009570854 | 19p13.3 | 0.043622441 |
hsa-miR-4327 | 2.33 | 0.00208623 | 21q22.11 | 0.016612376 |
hsa-miR-4538 | 2.21 | 0.016769506 | 14q32.33 | 0.062959199 |
hsa-miR-765 | 2.15 | 0.01548123 | 1q23.1 | 0.059425707 |
hsa-miR-937-5p | 2.11 | 6.85217E-05 | 8q24.3 | 0.002053966 |
hsa-miR-4653-3p | 2.10 | 0.006521157 | 7q22.1 | 0.034671494 |
hsa-miR-4746-3p | 2.08 | 0.001577889 | 19p13.3 | 0.01392446 |
hsa-miR-371b-5p | 2.07 | 0.000340744 | 19q13.42 | 0.004781581 |
hsa-miR-92b-5p | 2.06 | 0.000206021 | 1q22 | 0.003391425 |
hsa-miR-1237-5p | 2.05 | 0.004806337 | 11q13.1 | 0.027987923 |
hsa-miR-4447 | 2.03 | 0.001493554 | 3q13.31 | 0.013638253 |
Downregulated | ||||
hsa-miR-431-3p | 0.09 | 7.05876E-05 | 14q32.2 | 0.002053966 |
hsa-miR-551b-3p | 0.18 | 3.55933E-06 | 3q26.2 | 0.000917897 |
hsa-miR-4271 | 0.30 | 0.000111417 | 3p21.31 | 0.002316916 |
hsa-miR-181a-2-3p | 0.32 | 0.000142642 | 9q33.3 | 0.002713359 |
hsa-miR-612 | 0.38 | 0.00102969 | 11q13.1 | 0.011157148 |
hsa-miR-1273h-5p | 0.39 | 0.002814441 | 16p12.1 | 0.020416622 |
hsa-miR-760 | 0.39 | 0.000827908 | 1p22.1 | 0.009576883 |
hsa-miR-192-5p | 0.39 | 3.52356E-05 | 11q13.1 | 0.001651115 |
hsa-miR-210-3p | 0.40 | 0.001969138 | 11p15.5 | 0.016207521 |
hsa-miR-6872-3p | 0.42 | 1.83967E-05 | 3p21.31 | 0.00136536 |
hsa-let-7f-1-3p | 0.42 | 0.008961426 | 9q22.32 | 0.041607982 |
hsa-miR-1290 | 0.43 | 0.010000273 | 1p36.13 | 0.044817978 |
hsa-miR-4324 | 0.43 | 0.029330891 | 19q13.33 | 0.090639866 |
hsa-miR-4701-5p | 0.44 | 0.000306936 | 12q13.12 | 0.004529948 |
hsa-miR-4796-5p | 0.45 | 0.015071207 | 3q13.31 | 0.058375353 |
hsa-miR-593-3p | 0.45 | 0.001221347 | 7q32.1 | 0.012446109 |
hsa-miR-1287-5p | 0.47 | 0.000148136 | 10q24.2 | 0.002756624 |
hsa-miR-6776-3p | 0.48 | 0.001494273 | 17p13.3 | 0.013638253 |
hsa-miR-6870-3p | 0.48 | 0.003873881 | 20p12.2 | 0.024658098 |
hsa-miR-1178-3p | 0.49 | 0.021002746 | 12q24.23 | 0.072979103 |
hsa-miR-585-5p | 0.49 | 0.021434077 | 5q35.1 | 0.073606371 |
hsa-miR-6789-3p | 0.49 | 1.91406E-05 | 19p13.3 | 0.00136536 |
hsa-miR-5572 | 0.50 | 0.013211437 | 15q25.1 | 0.05284575 |
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Matsui, T.; Chiyo, T.; Kobara, H.; Fujihara, S.; Fujita, K.; Namima, D.; Nakahara, M.; Kobayashi, N.; Nishiyama, N.; Yachida, T.; et al. Telmisartan Inhibits Cell Proliferation and Tumor Growth of Esophageal Squamous Cell Carcinoma by Inducing S-Phase Arrest In Vitro and In Vivo. Int. J. Mol. Sci. 2019, 20, 3197. https://doi.org/10.3390/ijms20133197
Matsui T, Chiyo T, Kobara H, Fujihara S, Fujita K, Namima D, Nakahara M, Kobayashi N, Nishiyama N, Yachida T, et al. Telmisartan Inhibits Cell Proliferation and Tumor Growth of Esophageal Squamous Cell Carcinoma by Inducing S-Phase Arrest In Vitro and In Vivo. International Journal of Molecular Sciences. 2019; 20(13):3197. https://doi.org/10.3390/ijms20133197
Chicago/Turabian StyleMatsui, Takanori, Taiga Chiyo, Hideki Kobara, Shintaro Fujihara, Koji Fujita, Daisuke Namima, Mai Nakahara, Nobuya Kobayashi, Noriko Nishiyama, Tatsuo Yachida, and et al. 2019. "Telmisartan Inhibits Cell Proliferation and Tumor Growth of Esophageal Squamous Cell Carcinoma by Inducing S-Phase Arrest In Vitro and In Vivo" International Journal of Molecular Sciences 20, no. 13: 3197. https://doi.org/10.3390/ijms20133197