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| Screening anti-pituitary adenoma drugs from global marketed drug data based on artificial intelligence and validating with in vitro experiments |
| LYU Tingting, ZHANG Zirui, LI Shang, SUN Lan, DU Guanhua |
（Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China）
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Abstract Objective: Exploring potential treatment drugs for pituitary adenoma from marketed drugs based on artificial intelligence technology and drug relocation strategies. Methods: The gene expression profile of pituitary adenoma was analyzed by Gene Expression Omnibus （GEO） database, and the highest scoring Hub gene was screened out. The drug repositioning strategy was used to find therapeutic drugs targeting Hub gene from the global market drug database, and the interaction between drug and target was validated by artificial intelligence technology. In cell experiments, the effect of tamoxifen on the proliferation ability of mouse pituitary adenoma AtT20 cells and rat pituitary adenoma GH3 cells was detected by CCK8 method, the apoptosis rate was detected by flow cytometry, and the expressions of key proteins in the phosphatidylinositol-3-kinase （PI3K）/protein kinase B （AKT） apoptosis pathway was detected by Western blotting. Results: A total of 96 differentially expressed genes were identified from macroadenomas and microadenomas, among which signal transducer and activator of transcription 6 （STAT6） was the gene with the highest score. Tamoxifen was found to be the therapeutic drug targeting STAT6 by relocating from the database. The interaction between tamoxifen and STAT6 was confirmed by artificial intelligence and molecular docking. Finally, in vitro experiments showed that tamoxifen could inhibit the proliferation of pituitary adenoma cells and hormone secretion. Conclusion: Tamoxifen can inhibit the growth of pituitary adenoma, providing strong evidence for the target research and precise treatment of pituitary adenoma.
［Key words］pituitary adenoma; artificial intelligence; drug repositioning; STAT6; Tamoxifen
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Received: 08 December 2021
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| [1] |
. [J]. Journal of Jiangsu University(Medicine Edition), 2021, 31(01): 17-22. |
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