Glycyrrhizin mediates autophagy through the STAT3/survivin pathway to inhibit proliferation and angiogenesis in hepatoma cells

甘草酸通过STAT3/survivin通路介导自噬,从而抑制肝癌细胞的增殖和血管生成。

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Abstract

Liver cancer exhibits a covert onset, high propensity for recurrence and metastasis, ultimately leading to unfavourable prognosis and increased mortality. Glycyrrhizin (GL) exhibits diverse pharmacological activities and can serve as an autophagy inducer, thereby demonstrating its potential anticancer efficacy against various cancer cell types. The impact of GL on apoptosis, migration, the STAT3/Survivin pathway, and autophagy was analysed by administering GL to human hepatocellular carcinoma cell lines. Human liver cancer cell lines were treated with 3-MA (an autophagy inhibitor) and colivelin (STAT3 agonist) to analyze glycyrrhetin's effects on autophagy, angiogenesis, and the STAT3/Survivin pathway. The GL group showed significant decreases in cell proliferation, migration, and levels of p-STAT3, Survivin, LC3-I, P62, and VEGF-A compared to controls. Conversely, apoptosis rates and expressions of LC3-II and Beclin1 increased. In the 3-MA group, proliferation, migration, p-STAT3, Survivin, LC3-I, P62, and VEGF-A were higher than in controls, but apoptosis rates and LC3-II and Beclin1 levels were lower. Colivelin inhibited GL's effects, while GL countered 3-MA's actions. Supernatants from various cell groups also yielded similar results in Human umbilical vein endothelial cells (HUVECs). Thus, GL has ability to hinder the STAT3/Survivin signalling pathway, consequently fostering autophagy and delaying the onset and progression of liver cancer cell.

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