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绞股蓝单体苷 LI 抑制黑素瘤细胞增殖并上调 miR-128-3p 的表达。

Monomer gypenoside LI from Gynostemma pentaphyllum inhibits cell proliferation and upregulates expression of miR-128-3p in melanoma cells.

机构信息

Department of Biochemistry, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China.

School of Pharmacy, Minzu University of China, Beijing, China.

出版信息

J Biochem Mol Toxicol. 2020 May;34(5):e22460. doi: 10.1002/jbt.22460. Epub 2020 Feb 5.

DOI:10.1002/jbt.22460
PMID:32022984
Abstract

Gypenosides have anticancer activity against many cancers. Gypenoside LI is a gypenoside monomer from Gynostemma pentaphyllum, its pharmacological functions in melanoma have not been reported. In this study, we found that gypenoside LI had a potent cytotoxic effect on melanoma cells. Gypenoside LI can induce intrinsic apoptosis along with S phase arrest. Furthermore, gypenoside LI inhibited the colony formation ability of melanoma through inhibition of the Wnt/β-catenin signaling pathway. Interestingly, we also found that gypenoside LI can induce the upregulation of the tumor suppressor miR-128-3p during melanoma apoptosis. In contrast, gypenoside LI induced apoptosis, cell cycle arrest, and inhibition of the Wnt/β-catenin signaling pathway, which were abolished by overexpression of the miR-128-3p inhibitor in A375 cells. Taken together, these results showed that gypenoside LI could inhibit human melanoma cells through inducing apoptosis, arresting cell cycle at the S phase and suppressing the Wnt/β-catenin signaling pathway in a miR-128-3p dependent manner.

摘要

绞股蓝苷具有多种抗癌活性。绞股蓝苷 LI 是绞股蓝中的一种绞股蓝苷单体,其在黑色素瘤中的药理作用尚未报道。在本研究中,我们发现绞股蓝苷 LI 对黑色素瘤细胞具有很强的细胞毒性作用。绞股蓝苷 LI 可以通过诱导细胞发生内在型凋亡并使细胞周期阻滞在 S 期,从而抑制黑色素瘤细胞的集落形成能力。此外,有趣的是,我们还发现绞股蓝苷 LI 可以在黑色素瘤细胞凋亡过程中诱导肿瘤抑制 miR-128-3p 的上调。相反,在 A375 细胞中过表达 miR-128-3p 抑制剂可消除绞股蓝苷 LI 诱导的细胞凋亡、细胞周期阻滞和 Wnt/β-catenin 信号通路的抑制。综上所述,这些结果表明绞股蓝苷 LI 可以通过诱导细胞凋亡、使细胞周期阻滞在 S 期以及抑制 Wnt/β-catenin 信号通路来抑制人黑色素瘤细胞,这种作用是依赖于 miR-128-3p 的。

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