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表没食子儿茶素没食子酸酯(Theasaponin E₁)对 ALDH 阳性卵巢癌干细胞的抗增殖作用。

Anti-Proliferation Effect of Theasaponin E₁ on the ALDH-Positive Ovarian Cancer Stem-Like Cells.

机构信息

Department of Tea Science, Zhejiang University, Hangzhou 310058, China.

College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA.

出版信息

Molecules. 2018 Jun 17;23(6):1469. doi: 10.3390/molecules23061469.

Abstract

Ovarian cancer has the highest mortality rate of all gynecological malignancies and the five-year death rate of patients has remained high in the past five decades. Recently, with the rise of cancer stem cells (CSCs) theory, an increasing amount of research has suggested that CSCs give rise to tumor recurrence and metastasis. Theasaponin E₁ (TSE₁), which was isolated from green tea () seeds, has been proposed to be an effective compound for tumor treatment. However, studies on whether TSE₁ takes effect through CSCs have rarely been reported. In this paper, ALDH-positive (ALDH+) ovarian cancer stem-like cells from two platinum-resistant ovarian cancer cell lines A2780/CP70 and OVCAR-3 were used to study the anti-proliferation effect of TSE₁ on CSCs. The ALDH+ cells showed significantly stronger sphere forming vitality and stronger cell migration capability. In addition, the stemness marker proteins CD44, Oct-4, Nanog, as well as Bcl-2 and MMP-9 expression levels of ALDH+ cells were upregulated compared with the original tumor cells, indicating that they have certain stem cell characteristics. At the same time, the results showed that TSE₁ could inhibit cell proliferation and suspension sphere formation in ALDH+ cells. Our data suggests that TSE₁ as a natural compound has the potential to reduce human ovarian cancer mortality. However, more research is still needed to find out the molecular mechanism of TSE₁-mediated inhibition of ALDH+ cells and possible drug applications on the disease.

摘要

卵巢癌是妇科恶性肿瘤中死亡率最高的,过去五十年间患者的五年死亡率一直居高不下。最近,随着癌症干细胞(CSC)理论的兴起,越来越多的研究表明 CSCs 导致肿瘤复发和转移。茶皂素 E₁(TSE₁)是从绿茶()种子中分离出来的,被认为是一种有效的肿瘤治疗化合物。然而,关于 TSE₁ 是否通过 CSCs 发挥作用的研究很少有报道。在本文中,使用两种铂耐药卵巢癌细胞系 A2780/CP70 和 OVCAR-3 的 ALDH+(ALDH+)卵巢癌类干细胞样细胞来研究 TSE₁ 对 CSCs 的抗增殖作用。ALDH+细胞表现出明显更强的球体形成活力和更强的细胞迁移能力。此外,与原始肿瘤细胞相比,ALDH+细胞中的干细胞标记蛋白 CD44、Oct-4、Nanog 以及 Bcl-2 和 MMP-9 的表达水平上调,表明它们具有一定的干细胞特征。同时,结果表明 TSE₁ 可抑制 ALDH+细胞的增殖和悬浮球形成。我们的数据表明,TSE₁ 作为一种天然化合物有可能降低人类卵巢癌的死亡率。然而,仍需要进一步研究以确定 TSE₁ 介导的 ALDH+细胞抑制的分子机制以及该药物在该疾病中的可能应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff79/6100606/4ff62a6015b8/molecules-23-01469-g001.jpg

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