Anti-colorectal cancer targets of resveratrol and biological molecular mechanism: Analyses of network pharmacology, human and experimental data
Anti-colorectal cancer targets of resveratrol and biological molecular mechanism: Analyses of network pharmacology, human and experimental data
复制标题
DOI：
10.1002/jcb.28404
复制
发表时间：
2019-07-01
影响因子：
4
通讯作者：
Zhou, Liming
中科院分区：
文献类型：
--
作者：
Li, Rong;Ma, Xiuying;Zhou, Liming
在这项研究中，结直肠癌（CRC）疾病的目标和白藜芦醇（Res）相关的目标相结合，并通过使用分组数据库来识别预测的目标。在构建了Res抗CRC的靶点-功能蛋白相互作用网络后，通过拓扑分析构建了Res抗CRC的核心靶点。对所有核心靶点进行生物学功能和途径富集分析，优化Res抗CRC的生物学过程和关键信号通路。Res抗CRC的5个核心治疗靶点分别为蛋白激酶B1（AKT 1）、白细胞介素6（IL 6）、肿瘤蛋白p53（TP 53）、血管内皮生长因子和丝裂原活化蛋白激酶1。Res抗CRC的生物学过程主要与调节细胞凋亡、免疫应答、细胞通讯、信号转导和核素代谢有关。此外，前10个关键信号通路被确定，分别。在人类CRC样本分析中，CRC组织切片显示AKT 1和IL 6蛋白表达升高，伴有血液分子的异常变化。在Res抗结直肠癌的体外药理实验中，Res处理的HCT 116细胞表现出抑制细胞生长，诱导细胞死亡。此外，在RES处理的HCT 116细胞中，检查了细胞内AKT 1和IL 6表达的下调。总之，这些生物信息学发现和初步验证的数据揭示了与Res抗CRC相关的药理学分子机制，并进一步确定了五大核心治疗靶点。有利的是，这五个预测的靶点可能作为抗CRC治疗的潜在生物分子。
In this study, colorectal cancer (CRC)-diseased targets and resveratrol (Res)-associated targets were combined and constructed by the use of grouped databases for identification of the predicted targets. After production of target-functional protein interaction network of Res anti-CRC, the topological analysis was used to create the core targets of Res anti-CRC. All core targetsperformed the analyses of biological function and pathway enrichment to optimize the biological processes and key signaling pathways of Res anti-CRC. The resultant five core therapeutic targets of Res anti-CRC were identified as protein kinase B1 (AKT1), interleukin 6 (IL6), Tumor protein p53 (TP53), vascular endothelial growth factor, and mitogen-activated protein kinase 1, respectively. Biological processes of Res anti-CRC were predominantly associated with regulating apoptosis, immune response, cellular communication, signal transduction, and metabolism of the nuclide. In addition, the top 10 key signaling pathways were identified, respectively. In human CRC sample assays, CRC histologic sections showed elevated expression of AKT1 and IL6 proteins, accompanied with abnormal changes in blood molecules. In pharmacological experiments of Res anti-CRC in vitro, Res-treated HCT116 cells showed inhibited cell growth, induced cell death. In addition, downregulation of intracellular AKT1 and IL6 expression were checked in Res-treated HCT116 cells. Taken together, these bioinformatic findings and preliminary validated data uncovered pharmacological molecular mechanisms associated with Res anti-CRC, and further identified top five core therapeutic targets. Beneficially, these five predicted targets might serve as potential biomolecules for anti-CRC treatment.