Sorbonne Université, CNRS, IPCM, UMR 8232, 4 place Jussieu, 75005 Paris, France.
School of Pharmacy, Fuijan Provincial Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University, Fuzhou, Fujian 350122, China.
Eur J Med Chem. 2019 Mar 1;165:107-114. doi: 10.1016/j.ejmech.2019.01.016. Epub 2019 Jan 9.
Ganglioside GM3, belonging to glycosphingolipid family, has been known as tumor-associated carbohydrate antigen on several types of tumor. Many studies have revealed that GM3 plays a role in cell proliferation, adhesion and differentiation, which is crucial in the process of cancer development. In the present study, we firstly synthesized novel mannose-containing GM3 analogues by enzymatic hydrolysis and chemical procedures. Then the antiproliferative activity of the novel analogues along with galactose-containing analogues we prepared previously was investigated and the data demonstrated that these analogues exhibited antiproliferative effect on K562 and HCT116 cells. Finally, the influence of these analogues on tumor cell migration was studied on B16, B16-F10 and HCCLM3 cells by wound healing test, because the migration of tumor cells represents one of the relevant factors in assessing the malignancy of cancer. This study could lay the foundation for optimizing leading compounds and provide valuable information for finding new antitumor drugs for cancer therapy.
神经节苷脂 GM3 属于糖脂家族，已被确认为多种类型肿瘤的肿瘤相关碳水化合物抗原。许多研究表明，GM3 在细胞增殖、黏附和分化中发挥作用，这在癌症发展过程中至关重要。在本研究中，我们首先通过酶解和化学方法合成了新型含甘露糖的 GM3 类似物。然后研究了新型类似物以及我们之前制备的含半乳糖的类似物的抗增殖活性，数据表明这些类似物对 K562 和 HCT116 细胞具有抗增殖作用。最后，通过划痕实验研究了这些类似物对 B16、B16-F10 和 HCCLM3 细胞的肿瘤细胞迁移的影响，因为肿瘤细胞的迁移是评估癌症恶性程度的相关因素之一。这项研究为优化先导化合物奠定了基础，并为寻找癌症治疗的新型抗肿瘤药物提供了有价值的信息。
