Abstract The overexpression of sialic acids and sialyltransferases (STs) during malignant transformation and progression could result in the aberrant sialylation of cancer cells. Therefore, interfering the sialic acid synthesis might be an effective pathway in cancer therapy. In this study, we assessed that the antitumor inhibitors of 20(S)-ginsenosides Rg3, 20(R)-ginsenosides Rg3, 20(S)-ginsenosides Rh2, and 20(R)-ginsenosides Rh2 could block the sialoglycans in liver cancer cells HepG2. The results showed that these four compounds could inhibit the expressions of the total and free sialic acid at different levels in HepG2, respectively; also, it showed dose dependence. In addition, the results of the enzyme-linked immunosorbent assay showed that the above four compounds can inhibit the expression of STs significantly. We also found that these compounds could mediate the block of sialylation of α2,3- and α2,6-linked sialic acids in HepG2 cells by flow cytometry. Meanwhile, the results of the molecular docking investigation showed that these compounds showed strong interaction with ST6GalI and ST3GalI. These results verified that the ginsenosides have a powerful inhibiting aberrant sialylation, and it laid a theoretical foundation for further research on the investigation of ginsenosides as the target inhibitors on STs.

中文翻译：

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人参皂苷，唾液酸转移酶的强效抑制剂

摘要 恶性转化和进展过程中唾液酸和唾液酸转移酶（STs）的过度表达可能导致癌细胞的异常唾液酸化。因此，干扰唾液酸合成可能是癌症治疗的有效途径。在本研究中，我们评估了 20(S)-人参皂苷 Rg3、20(R)-人参皂苷 Rg3、20(S)-人参皂苷 Rh2 和 20(R)-人参皂苷 Rh2 的抗肿瘤抑制剂可以阻断肝癌中的唾液酸聚糖细胞 HepG2。结果表明，这4种化合物分别对HepG2中总唾液酸和游离唾液酸的表达有不同程度的抑制作用；此外，它还表现出剂量依赖性。此外，酶联免疫吸附试验结果表明，上述四种化合物均能显着抑制STs的表达。我们还发现，这些化合物可以通过流式细胞术介导 HepG2 细胞中α2,3-和α2,6-连接的唾液酸的唾液酸化阻断。同时，分子对接研究结果表明，这些化合物与 ST6GalI 和 ST3GalI 显示出强烈的相互作用。这些结果证实了人参皂苷具有很强的抑制异常唾液酸化的作用，为进一步研究人参皂苷作为STs的靶向抑制剂奠定了理论基础。