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翻白草通过下调 Akt/mTOR 信号通路对脑胶质瘤癌细胞的增殖抑制作用。

Antiproliferative effect of Potentilla fulgens on glioblastoma cancer cells through downregulation of Akt/mTOR signaling pathway.

机构信息

Department of Medical Biology, Faculty of Medicine, Dicle University, Diyarbakır, Turkey.

Cancer Research Center, Dicle University, Diyarbakır, Turkey.

出版信息

J Cancer Res Ther. 2023 Oct 1;19(7):1818-1824. doi: 10.4103/jcrt.jcrt_1886_21. Epub 2022 Jul 15.

Abstract

BACKGROUND

Glioblastoma multiforme (GBM) is the most aggressive brain tumor that is common among adults. This aggression is due to increased invasion, migration, proliferation, angiogenesis, and decreased apoptosis. Plant-based compounds have a high potential to be used as an anticancer agent due to their various mechanisms and less undesirable side effects. Potentilla fulgens is a medicinal plant, and methanolic root extract of P. fulgens (PRE) has anti-inflammatory and anticancer properties.

OBJECTIVE

In this study, we aimed to investigate antiproliferative effect of PRE on U118 and T98G glioblastoma cancer cells and to reveal which molecular signaling pathways regulate this mechanism of action.

MATERIALS AND METHODS

The effect of PRE on cell viability of GBM cells was investigated by MTT assay. Involvement of PRE with cell growth and survival signaling pathways, phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR and c-Src/signal transducer and activator of transcription 3 (STAT3), was examined using Western Blot.

RESULTS

PRE reduced cell viability of GBM and human dermal fibroblast (HDF) cells in a dose-and time-independent manner. PI3K expression/phosphorylation level remained unchanged in both GBM and HDF cells after PRE treatment, but Akt/mTOR signaling pathway was downregulated in PRE-treated cells. PRE treatment did not affect c-Src expression/phosphorylation level in GBM cells; however, expression of c-Src was suppressed in HDF cells. Similar results were observed for STAT3 expression and phosphorylation status.

CONCLUSION

PRE has the ability to suppress cell viability in GBM cells, by targeting the Akt/mTOR signaling pathway.

摘要

背景

多形性胶质母细胞瘤(GBM)是成人中常见的最具侵袭性的脑肿瘤。这种侵袭性归因于侵袭、迁移、增殖、血管生成的增加和细胞凋亡的减少。植物化合物由于其多种机制和较少的不良副作用,具有很高的用作抗癌剂的潜力。翻白草是一种药用植物,翻白草的甲醇根提取物(PRE)具有抗炎和抗癌特性。

目的

在这项研究中,我们旨在研究 PRE 对 U118 和 T98G 胶质母细胞瘤癌细胞的增殖抑制作用,并揭示哪些分子信号通路调节这种作用机制。

材料和方法

通过 MTT 测定法研究 PRE 对 GBM 细胞活力的影响。使用 Western Blot 检查 PRE 与细胞生长和存活信号通路(磷脂酰肌醇 3-激酶(PI3K)/Akt/mTOR 和 c-Src/信号转导和转录激活因子 3(STAT3))的关系。

结果

PRE 以剂量和时间非依赖性方式降低 GBM 和人真皮成纤维细胞(HDF)细胞的活力。PRE 处理后,GBM 和 HDF 细胞中的 PI3K 表达/磷酸化水平保持不变,但 Akt/mTOR 信号通路在 PRE 处理的细胞中被下调。PRE 处理不影响 GBM 细胞中 c-Src 的表达/磷酸化水平;然而,在 HDF 细胞中 c-Src 的表达受到抑制。STAT3 的表达和磷酸化状态也观察到类似的结果。

结论

PRE 通过靶向 Akt/mTOR 信号通路,具有抑制 GBM 细胞活力的能力。

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