Screening of alternative drugs to the tumor suppressor miR-375 in esophageal squamous cell carcinoma using the connectivity map.
| Autor: | Isozaki Y; Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Japan., Hoshino I, Akutsu Y, Hanari N, Mori M, Nishimori T, Murakami K, Akanuma N, Toyozumi T, Takahashi M, Suito H, Takeshita N, Maruyama T, Suzuki A, Nakayama T, Matsubara H |
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| Jazyk: | angličtina |
| Zdroj: | Oncology [Oncology] 2014; Vol. 87 (6), pp. 351-63. Date of Electronic Publication: 2014 Sep 05. |
| DOI: | 10.1159/000365592 |
| Abstrakt: | Objective: The aim of this study was to identify alternative compounds to the tumor suppressor miR-375 using the connectivity map (CMAP) and to validate the antitumor effects of the identified drugs in esophageal squamous cell carcinoma (ESCC). Methods: Gene profiling of miR-375-treated TE2 and T.Tn cells was applied in order to search the CMAP database. Among the compounds identified using the CMAP, we focused on 8 drugs [(-)-epigallocatechin-3-gallate, metformin, rosiglitazone among others], excluding 2 drugs among the top 10 compounds. We evaluated whether these compounds possess tumor-suppressive functions in ESCC. Results: A cytotoxicity assay showed that the sensitivity of TE2 and T.Tn cells treated with the 8 compounds was evaluated based on IC50 values of 42.9 µM to 3.8 mM. A cell cycle analysis revealed that the percentage of TE2 and T.Tn cells incubated with 6 compounds in the G0/G1 phase or the G2/M phase increased by approximately 40-80%. A TUNEL assay showed that the percentages of apoptotic cells treated with almost all compounds were significantly increased (p < 0.05) compared with the control cells. Conclusion: The CMAP database is a useful tool for identifying compounds affecting the same molecular pathways, particularly products that are difficult to apply via practical approaches, such as microRNAs. (© 2014 S. Karger AG, Basel.) |
| Databáze: | MEDLINE |
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