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OSW-1 诱导肝癌细胞凋亡和坏死的信号转导网络。

Signaling network of OSW‑1‑induced apoptosis and necroptosis in hepatocellular carcinoma.

机构信息

Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Yanbian University, Yanji, Jilin 133000, PR China.

出版信息

Mol Med Rep. 2013 May;7(5):1646-50. doi: 10.3892/mmr.2013.1366. Epub 2013 Mar 13.

Abstract

The compound 3β, 16β, 17α‑trihydroxycholest‑5‑en‑22‑one 16‑O‑(2‑O‑4‑methoxybenzoyl‑β‑D‑xylopyranosyl)‑ (1→3)‑(2‑O‑acetyl‑α‑L‑arabinopyranoside (OSW‑1) is a member of the cholestane saponin family that was created in the bulbs of Ornithogalum saudersiae. OSW‑1 has previously been shown as cytotoxic against numerous types of malignant cells, however, its antitumoral mechanisms remain unclear. The present study aimed to examine the potential changes in the gene expression of a hepatocellular carcinoma (HCC) cell line (Hep3B) incubated with OSW‑1 in vitro. The results showed that OSW‑1 inhibited tumors through invasiveness, angiogenesis, cell polarity and cell adhesion (as shown by Roche NimbleGen gene expression analysis), in addition to inducing apoptosis through the mitochondrial pathway. This affected the expression of a number of core genes in a number of signaling pathways, including WNT, MAPK, VEGF and P53. To the best of our knowledge, the present study is the first to report that OSW‑1, as a molecular compound, induces necroptotic death in hepatocellular carcinoma (HCC).

摘要

化合物 3β,16β,17α-三羟基胆甾-5-烯-22-酮 16-O-(2-O-4-甲氧基苯甲酰基-β-D-吡喃木糖基)-(1→3)-(2-O-乙酰基-α-L-阿拉伯吡喃糖苷(OSW-1)是一种胆甾烷皂苷家族的成员,它是在奥氏鹤望兰的鳞茎中合成的。OSW-1 先前已被证明对多种类型的恶性细胞具有细胞毒性,但它的抗肿瘤机制尚不清楚。本研究旨在研究体外孵育 OSW-1 对肝癌细胞系(Hep3B)的基因表达可能发生的变化。结果表明,OSW-1 通过侵袭、血管生成、细胞极性和细胞黏附(如罗氏 NimbleGen 基因表达分析所示)抑制肿瘤生长,此外还通过线粒体途径诱导细胞凋亡。这影响了包括 WNT、MAPK、VEGF 和 P53 在内的许多信号通路中的许多核心基因的表达。据我们所知,本研究首次报道 OSW-1 作为一种分子化合物,诱导肝癌(HCC)发生坏死性细胞死亡。

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