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Anti-tumour effects of beta-sitosterol are mediated by AMPK/PTEN/HSP90 axis in AGS human gastric adenocarcinoma cells and xenograft mouse models

机译:β-谷甾醇的抗肿瘤作用由AGS人胃腺癌细胞和异种移植小鼠模型中的AMPK / PTEN / HSP90轴介导

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摘要

We investigated the anti-cancer effects of beta-sitosterol (BS), a plant-derived sterol in AGS human gastric adenocarcinoma cells and xenograft mouse models. BS significantly reduced cell viability by inducing apoptosis in AGS adenocarcinoma cells. This was accompanied by the formation of apoptotic bodies, as detected by Annexin V, caspase 3/7 activity, and MitoPotential assay. BS stimulated phosphatase and tensin homolog (PTEN) and phospho-AMP-activated protein kinase (p-AMPK) expression. Pharmacological inhibitors or siRNA were used to further analyse the relationship between the two proteins. AMPK was found to represent a likely upstream regulator of PTEN. Additionally, two-dimensional gel electrophoresis was used to identify related proteins in the treatment of BS. The decrease of Hsp90 protein by BS was observed. Induction of PTEN protein and reduction of Hsp90 was mediated by AICAR, an AMPK activator, indicating that AMPK is necessary for PTEN and Hsp90 expression. Additionally, BS was found to be effective through the regulation of cancer biomarker. Furthermore, BS suppressed tumour growth without toxicity in the AGS xenograft mouse models-. Taken together, the present results demonstrate that BS exerts anti-cancer effects in AGS cells and xenograft mouse models by mediating AMPK, PTEN, and Hsp90.
机译:我们调查了β-谷甾醇(BS)的抗癌作用,植物衍生的甾醇在AGS人胃腺癌细胞和异种移植小鼠模型中。 BS通过在AGS腺癌细胞中诱导细胞凋亡而显着降低细胞活力。这伴随着凋亡体的形成,如附睾v,caspase 3/7活性检测到的凋亡体和暗症测定。 BS刺激磷酸酶和硫素同源物(PTEN)和磷酸-AMP-活化蛋白激酶(P-AMPK)表达。药理学抑制剂或siRNA用于进一步分析两种蛋白质之间的关系。发现安培代表了PTEN的一个可能上游调节器。另外,使用二维凝胶电泳用于鉴定BS治疗中的相关蛋白质。观察到BS的HSP90蛋白质的降低。 PTEN蛋白的诱导和HSP90的减少由AICAR,AMPK活化剂介导,表明AMPK是PTEN和HSP90表达所必需的。此外,发现BS通过调节癌症生物标志物而有效。此外,BS在AGS异种移植小鼠模型中抑制肿瘤生长而没有毒性 - 。在一起,目前的结果表明BS通过介导AMPK,PTEN和HSP90对AGS细胞和异种移植小鼠模型中的抗癌作用产生抗癌作用。

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