半乳糖凝集素-1在二甲双胍抑制胆管癌细胞增殖中的作用和机制

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Abstract Objective To investigate the role and molecular mechanism of galactose lectin-1(Galectin-1, Gal-1) in the inhibition of cholangiocarcinoma cell proliferation by metformin. Methods HuCCT1 cells were treated with different doses of metformin for 24, 48 and 72 h. The effect of metformin on cell survival was detected by CCK8, and cells were treated with 0 and 20 mmol /L of metformin for 24 h. The effects of metformin on cell clone formation, cell cycle and apoptotic vesicles were analyzed by clone formation assay, flow cytometry and DAPI staining. The expression of Gal-1 in cholangiocarcinoma and its effect on the survival rate of cholangiocarcinoma patients were analyzed using TCGA, GEPIA, UALCAN, HPA and other databases; the expression changes of Gal-1 in intrahepatic cholangiocarcinoma tissues and paracancerous tissues were detected by immunohistochemistry; cells were treated with 0 and 20 mmol /L metformin for 24 h, and Gal-1 and the protein PI3K, which is closely related to cell proliferation, were detected using Western Blot. The cells were treated with 0 and 20 mmol/L metformin for 24 h. The protein expression of Gal-1 and closely related proteins PI3K, AKT and mTOR were detected by Western Blot. Results The cell survival rate decreased significantly with the increase of metformin treatment concentration and treatment time, and the results of clone formation assay showed that the clone formation rates of control and 20 mmol/L metformin treated groups were 18.17% and 1.98%, respectively. The metformin treated groups showed significant G2 phase cell block and were accompanied by the formation of a large number of apoptotic vesicles. The results of biochemical analysis showed that Gal-1 expression was significantly increased in cholangiocarcinoma cells, and the results of immunohistochemistry using cancer and paraneoplastic tissues were consistent with the results of biochemical analysis, and the high expression of Gal-1 was closely associated with OS in cholangiocarcinoma patients; the expression of Gal-1 was significantly decreased in metformin-treated HuCCT1 cells, and accompanied by the inhibition of PI3K/AKT signaling pathway; in addition , inhibition of Gal-1 expression not only reduced cell proliferation ability but also restricted the inhibition of PI3K/AKT signaling pathway. Conclusion Metformin can inhibit the activation of PI3K/AKT signaling pathway by suppressing Gal-1 expression in intrahepatic cholangiocarcinoma, which in turn leads to the inhibition of cell proliferation.

Key words： metformin intrahepatic cholangiocarcinoma Gal-1 PI3K/AKT

Received: 09 December 2022

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	SHI Rong
	MO Hanlin
	LI Yangbo
	ZHANG Zhibai
	LI Hao

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SHI Rong,MO Hanlin,LI Yangbo等. Role and mechanism of galactoglutinin-1 in metformin inhibition of proliferation of cholangiocarcinoma cells[J]. HuNan ShiFan DaXue XueBao(YiXueBan), 2023, 20(1): 18-23.

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http://yxb.hunnu.edu.cn/EN/ OR http://yxb.hunnu.edu.cn/EN/Y2023/V20/I1/18

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