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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

虫草素下调Cdk-2干扰细胞周期并通过在宫颈癌细胞中产生ROS来增加细胞凋亡：体外和计算机研究

卷 19, 期 2, 2019

页: [152 - 159] 页: 8

弟呕挨: 10.2174/1568009618666180905095356

价格: $65

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摘要

背景：虫草素是一种来自药用蘑菇冬虫夏草的小分子，据报道它具有抗癌特性。目的：在本研究中，我们重点研究了虫草素对宫颈癌细胞的影响，并进一步阐明了可能的分子机制。 方法：采用细胞活力和细胞计数法检测虫草素的细胞毒作用，流式细胞术检测细胞凋亡和细胞周期，定量PCR（qPCR）和Western blotting检测靶基因的表达。分子对接和分子动力学模拟用于计算机分析虫草素对靶蛋白的亲和力。 结果：虫草素处理控制SiHa和HeLa宫颈癌细胞生长，增加其凋亡率，干扰细胞周期，特别是拉长S期。 qPCR结果表明通过虫草素处理在mRNA水平上存在细胞周期蛋白CDK-2，CYCLIN-A2和CYCLIN-E1的下调，但在促凋亡蛋白或抗凋亡蛋白中未观察到显着变化。虫草素处理细胞的细胞内活性氧（ROS）水平显着增加，这意味着ROS可能诱导细胞凋亡。蛋白质印迹分析证实虫草素可显着降低Cdk-2，并使Cyclin-E1和Cyclin-A2轻度下降，这可能是调节细胞周期的原因。分子对接表明虫草素对Cdk-2具有高结合亲和力。分子动力学模拟进一步证实，虫草素-Cdk-2复合物的对接姿势保持在结合口袋内10ns。 结论：我们的研究表明虫草素对宫颈癌细胞有效，通过细胞周期蛋白调节细胞周期，特别是下调Cdk-2，通过产生ROS诱导细胞凋亡是虫草素抗癌活性的机制之一。

关键词: 虫草素，宫颈癌，细胞凋亡，活性氧，细胞周期，Cdk-2

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