Gao Liping, Shen Li, Yu Meiyun, Ni Jianlong, Dong Xiaoxia, Zhou Yinghui, Wu Shiliang
Department of Biochemistry and Molecular Biology, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
Mol Med Rep. 2014 May;9(5):1697-702. doi: 10.3892/mmr.2014.2008. Epub 2014 Mar 5.
5-Fluorouracil (5-FU) is the major chemotherapeutic agent for the treatment of colorectal carcinoma, which were found to have N-glycans containing polylactosamine on the cancer cell surface. Alterations in the expression and structure of polylactosamine glycans are associated with cellular differentiation and oncogenesis. However, little is known with regard to the correlation between the levels of polylactosamine expressed in colon cancer cells and the anticancer effect of 5-FU. In the present study, SW620 cells were treated with the half maximal inhibitory concentration (IC50; determined by MTT-assay) of 5-FU. Hoechst 33258 staining and flow cytometric analysis indicated that 5-FU administration resulted in apoptosis in SW620 cells. An increased percentage of cells in S phase was also observed among the SW620 cells treated with 5-FU. Under the same experimental conditions, a decrease in the 5-FU‑induced inhibition of polylactosamine glycans was recorded. However, an increase in the activity of alkaline phosphatase was also observed. Furthermore, pretreatment of the SW620 cells with 5-FU inhibited the expression of β1,3-N-acetylglucosaminyltransferase-8 (β3Gn-T8) and cluster of differentiation (CD)147 in a time-dependent manner. Overall, changes in glycosylation were associated with the anticancer effect of 5-FU in the colon cancer cells. In conclusion, polylactosamine may be a useful target for the identification of substances with anticancer activity.
5-氟尿嘧啶（5-FU）是治疗结直肠癌的主要化疗药物，研究发现癌细胞表面的N-聚糖含有多聚乳糖胺。多聚乳糖胺聚糖的表达和结构改变与细胞分化和肿瘤发生有关。然而，关于结肠癌细胞中多聚乳糖胺表达水平与5-FU抗癌效果之间的相关性知之甚少。在本研究中，用5-FU的半数最大抑制浓度（IC50；通过MTT法测定）处理SW620细胞。Hoechst 33258染色和流式细胞术分析表明，给予5-FU可导致SW620细胞凋亡。在用5-FU处理的SW620细胞中也观察到S期细胞百分比增加。在相同实验条件下，记录到5-FU诱导的多聚乳糖胺聚糖抑制作用降低。然而，也观察到碱性磷酸酶活性增加。此外，用5-FU预处理SW620细胞可时间依赖性地抑制β1,3-N-乙酰葡糖胺基转移酶-8（β3Gn-T8）和分化簇（CD）147的表达。总体而言，糖基化变化与5-FU对结肠癌细胞的抗癌作用有关。总之，多聚乳糖胺可能是鉴定具有抗癌活性物质的有用靶点。
