Soyasaponin-I-modified invasive behavior of cancer by changing cell surface sialic acids

Soyasaponin-I-modified invasive behavior of cancer by changing cell surface sialic acids
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DOI:
10.1016/j.ygyno.2004.10.010
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发表时间:
2005-02-01
影响因子:
4.7
通讯作者:
Tsai, YC
Tsai, YC
中科院分区:
医学2区
文献类型:
--
作者:
Hsu, CC;Lin, TW;Tsai, YC

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目标。涎酰基转移酶(ST)活性的改变与肿瘤的形成和侵袭行为密切相关。一种有效的ST抑制剂大豆皂苷I (Ssal)被发现可以选择性地抑制细胞α 2.3-唾液基转酶活性,本研究进一步测试了Ssal对癌细胞转移和侵袭行为的影响。以非转移性乳腺癌细胞系MCF-7和高转移性乳腺癌细胞系MDA-MB-231为研究对象,研究了Ssal油对肿瘤细胞的影响。Ssal不影响细胞生长周期,在本研究中也未能抑制细胞生长(Ssal浓度小于等于100 muM)。结果表明,Ssal可成功抑制细胞α 2,3- st活性,抑制剂量依赖性肿瘤细胞表面α 2.3-唾液酸的表达。此外,不同浓度的sal确实线性刺激MCF-7细胞对胶原带I的粘附,并显著增强细胞对Matrigel-matrix的粘附。此外,Ssal显著降低MDA-MB-231细胞迁移。逆转录酶聚合酶链反应评价ST3Gal I、III和IV mRNA的表达,结果显示,Ssal也下调了ST3Gal IV的表达,但对其他两者没有影响。结果表明,Ssal参与了肿瘤细胞的侵袭行为,表明α 2,3-唾液化途径的改变在肿瘤的粘附和转移中起着至关重要的作用。Ssal是研究st生物学作用的一个很好的候选者,可能为肿瘤转移的预防提供新的策略。(C) 2004爱思唯尔公司版权所有。
Objective. Sialylation involving tumor formation and invasive behavior goes along with altered sialyltransferase (ST) activity. A potent ST inhibitor, soyasaponin I (Ssal), was discovered to selectively inhibit the cellular alpha2.3-sialyltranserase activity In this study, we further test the effects of Ssal on modifing the metastatic and invasive behaviors of cancer cell lines.Methods. Nonmetastatic breast cancer cell line, MCF-7, and highly metastastic breast cancer cell line, MDA-MB-231, were used to investigate the effects of Ssal oil tumor cells.Results. Ssal did not affect cell growth cycle and also failed to inhibit cell growth in this study (the concentration of Ssal less than or equal to100 muM). Ssal was as predicted to successfully inhibit cellular alpha2,3-ST activity and depressed the dose-dependent tumor cell surface alpha2.3-sialic acid expression. In addition, different concentrations of Ssal did stimulate MCF-7 cell adhesion to collagen tape I linearly and significantly enhanced cell adhesion to the Matrigel-matrix. Furthermore, Ssal significantly decreased MDA-MB-231 cell migration. Reverse transcriptase polymerase chain reaction for evaluating mRNA expression of ST3Gal I,III and IV showed that Ssal also down-regulated the expression of ST3Gal IV but did not affect the other two.Conclusions. The results showed that Ssal was implicated in the invasive behavior of tumor cells, suggesting that altered alpha2,3-sialylation pathway played a crucial role in the adhesion and tumor metastases. Ssal is a good candidate for studying the biological roles of ST. and might provide a new preventive strategy in tumor metastasis. (C) 2004 Elsevier Inc. All rights reserved.