Department of Biochemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Comput Biol Chem. 2024 Oct;112:108178. doi: 10.1016/j.compbiolchem.2024.108178. Epub 2024 Aug 22.
Colorectal cancer (CRC) poses a significant global health challenge, characterized by substantial prevalence variations across regions. This study delves into the therapeutic potential of rutin, a polyphenol abundant in fruits, for treating CRC. The primary objectives encompass identifying molecular targets and pathways influenced by rutin through an integrated approach combining bioinformatic analysis and experimental validation. Employing Gene Set Enrichment Analysis (GSEA), the study focused on identifying potential differentially expressed genes (DEGs) associated with CRC, specifically those involved in regulating reactive oxygen species, metabolic reprogramming, cell cycle regulation, and apoptosis. Utilizing diverse databases such as GEO2R, CTD, and Gene Cards, the investigation revealed a set of 16 targets. A pharmacological network analysis was subsequently conducted using STITCH and Cytoscape, pinpointing six highly upregulated genes within the rutin network, including TP53, PCNA, CDK4, CCNEB1, CDKN1A, and LDHA. Gene Ontology (GO) analysis predicted functional categories, shedding light on rutin's potential impact on antioxidant properties. KEGG pathway analysis enriched crucial pathways like metabolic and ROS signaling pathways, HIF1a, and mTOR signaling. Diagnostic assessments were performed using UALCAN and GEPIA databases, evaluating mRNA expression levels and overall survival for the identified targets. Molecular docking studies confirmed robust binding associations between rutin and biomolecules such as TP53, PCNA, CDK4, CCNEB1, CDKN1A, and LDHA. Experimental validation included inhibiting colorectal cell HT-29 growth and promoting cell growth with NAC through MTT assay. Flow cytometric analysis also observed rutin-induced G1 phase arrest and cell death in HT-29 cells. RT-PCR demonstrated reduced expression levels of target biomolecules in HT-29 cells treated with rutin. This comprehensive study underscores rutin's potential as a promising therapeutic avenue for CRC, combining computational insights with robust experimental evidence to provide a holistic understanding of its efficacy.
结直肠癌（CRC）是一个全球性的健康挑战，其在不同地区的患病率存在显著差异。本研究探讨了芦丁作为水果中富含的多酚，治疗 CRC 的治疗潜力。主要目标是通过结合生物信息学分析和实验验证的综合方法，确定芦丁影响的分子靶点和途径。使用基因集富集分析（GSEA），研究集中于确定与 CRC 相关的潜在差异表达基因（DEGs），特别是涉及调节活性氧、代谢重编程、细胞周期调节和细胞凋亡的基因。通过 GEO2R、CTD 和 Gene Cards 等多个数据库，该研究确定了一组 16 个靶点。随后使用 STITCH 和 Cytoscape 进行了药理学网络分析，确定了芦丁网络中的六个高度上调基因，包括 TP53、PCNA、CDK4、CCNEB1、CDKN1A 和 LDHA。基因本体论（GO）分析预测了功能类别，揭示了芦丁对抗氧化特性的潜在影响。KEGG 通路分析富集了代谢和 ROS 信号通路、HIF1a 和 mTOR 信号等关键通路。使用 UALCAN 和 GEPIA 数据库进行诊断评估，评估了所鉴定靶点的 mRNA 表达水平和总生存期。分子对接研究证实了芦丁与 TP53、PCNA、CDK4、CCNEB1、CDKN1A 和 LDHA 等生物分子之间存在强大的结合关系。实验验证包括通过 MTT 测定法抑制结直肠细胞 HT-29 的生长和用 NAC 促进细胞生长。流式细胞术分析还观察到芦丁诱导 HT-29 细胞 G1 期停滞和细胞死亡。RT-PCR 表明 HT-29 细胞中芦丁处理后靶生物分子的表达水平降低。这项综合研究强调了芦丁作为 CRC 有前途的治疗途径的潜力，将计算见解与强大的实验证据相结合，提供了对其疗效的全面理解。
