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一种新型邻萘醌通过 AKT 信号通路抑制 N-钙黏蛋白表达并阻断黑色素瘤细胞侵袭。

A novel o-naphtoquinone inhibits N-cadherin expression and blocks melanoma cell invasion via AKT signaling.

机构信息

Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Corrêa 01-Guamá, Belém/PA, Brazil.

出版信息

Toxicol In Vitro. 2013 Oct;27(7):2076-83. doi: 10.1016/j.tiv.2013.07.011. Epub 2013 Aug 1.

Abstract

The down-regulation or loss of epithelial markers is often accompanied by the up-regulation of mesenchymal markers. E-cadherin generally suppresses invasiveness, whereas N-cadherin promotes invasion and metastasis in vitro. The aim of this work is to investigate the role of biflorin, a naphthoquinone with proven anticancer properties, on the expression of N-cadherin and AKT proteins in MDA-MB-435 invasive melanoma cancer cells after 12h of exposure to 1, 2.5 and 5 μM biflorin. Biflorin inhibited MDA-MB-435 invasion in a dose-dependent manner (p<0.01). Likewise, biflorin down-regulated N-cadherin and AKT-1 expression in a dose-dependent manner. Biflorin did not inhibit the adhesion of MDA-MB-435 cells to any tested substrates. Additionally, biflorin blocked the invasiveness of cells by down-regulating N-cadherin, most likely via AKT-1 signaling. As such, biflorin may be a novel anticancer agent and a new prototype for drug design.

摘要

上皮标志物的下调或缺失通常伴随着间充质标志物的上调。E-钙黏蛋白通常抑制侵袭性,而 N-钙黏蛋白促进体外侵袭和转移。本研究旨在探讨双花内脂(一种具有抗癌特性的萘醌)在 12 小时暴露于 1、2.5 和 5 μM 双花内脂后对 MDA-MB-435 侵袭性黑色素瘤癌细胞中 N-钙黏蛋白和 AKT 蛋白表达的影响。双花内脂呈剂量依赖性抑制 MDA-MB-435 的侵袭(p<0.01)。同样,双花内脂呈剂量依赖性地下调 N-钙黏蛋白和 AKT-1 的表达。双花内脂没有抑制 MDA-MB-435 细胞在任何测试基质上的黏附。此外,双花内脂通过下调 N-钙黏蛋白阻断细胞的侵袭性,这很可能是通过 AKT-1 信号通路。因此,双花内脂可能是一种新型抗癌药物,也是药物设计的新原型。

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