The Effects and Mechanism of Action of Small Molecule Inhibitors Targeting Galectin-3 on Intrahepatic Cholangiocarcinoma Cells

ZHANG Zhibai; LI Jiang; CAO Mengqiu; LI Hao

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Journal of Hunan Normal University(Medical Science) ›› 2025, Vol. 22 ›› Issue (5) : 35-41.

The Effects and Mechanism of Action of Small Molecule Inhibitors Targeting Galectin-3 on Intrahepatic Cholangiocarcinoma Cells

ZHANG Zhibai, LI Jiang, CAO Mengqiu, LI Hao

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Abstract

Objective This study aimed to identify small-molecule inhibitors targeting Galectin-3(Gal-3) based on machine learning techniques and to investigate their binding modes with Gal-3 as well as their effects on the proliferation and migration of intrahepatic cholangiocarcinoma (ICC) cells. Methods Bioinformatics and immunohistochemistry were used to analyze Gal-3 expression in ICC tissues and its correlation with prognosis. The structure of Gal-3 and the TargetMol L4000 compound library were preprocessed using Schrödinger software, followed by virtual screening through molecular docking. Candidate inhibitors were selected via clustering analysis and manual evaluation. ICC cell lines were treated with different concentrations of the inhibitors for 24 h and 48 h, and CCK-8, EdU, and wound healing assays were performed to assess cell viability, proliferation, and migration. Results Gal-3 was significantly overexpressed in ICC tissues and correlated with poor prognosis. Magnesium Lithospermate B (MLB) was identified as a potential Gal-3 inhibitor through virtual screening. In vitro experiments showed that MLB significantly inhibited ICC cell proliferation and migration. Conclusion Gal-3 is highly expressed in ICC and may serve as a therapeutic target. MLB, as a Gal-3 inhibitor, exhibits potential antitumor activity against ICC.

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intrahepatic cholangiocarcinoma / Gal-3 / molecule inhibitors / MLB

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ZHANG Zhibai, LI Jiang, CAO Mengqiu, LI Hao. The Effects and Mechanism of Action of Small Molecule Inhibitors Targeting Galectin-3 on Intrahepatic Cholangiocarcinoma Cells[J]. Journal of Hunan Normal University(Medical Science). 2025, 22(5): 35-41

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