Li Xiaochen, Ju Yang, Yang Xinxin, Li Tianjiao, Wang Shuai, Bao Yongrui, Meng Xiansheng
College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China.
Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, China.
Front Immunol. 2025 Aug 14;16:1631031. doi: 10.3389/fimmu.2025.1631031. eCollection 2025.
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with pro-tumor inflammation playing a critical role in its initiation and progression. Chronic inflammation acts as a major driving force and a distinct mechanism underlying tumorigenesis. Although previous studies have demonstrated the importance of the VEGF/p38MAPK and p38MAPK/HSP27 signaling pathways in CRC-associated inflammation, a comprehensive understanding of the entire pro-tumor inflammatory mechanism remains incomplete.
This study combined network pharmacology analysis and pharmacodynamic experiments using a p38MAPK pathway inhibitor to systematically identify and validate the VEGF/p38MAPK/HSP27 pro-tumor inflammatory signaling pathway. Western blotting was used to confirm key target proteins. Molecular docking and microscale thermophoresis (MST) experiments were conducted to screen active compounds from (PV). Molecular dynamics (MD) simulations evaluated the stability and drug-likeness of compound-target interactions.
Key proteins VEGF, p38MAPK, and HSP27 were identified as critical components of the signaling pathway. Three active compounds rutin, nicotiflorin, and 4,5-dicaffeoylquinic acid (4,5-Dicqa) were found to bind these targets with high affinity. MD simulations supported the stability of these interactions and their potential as drug candidates.
This study provides theoretical and experimental evidence for pharmacological targets involved in pro-tumor inflammation in CRC. The findings offer valuable insights for developing novel anti-inflammatory therapeutics targeting the VEGF/p38MAPK/HSP27 signaling pathway.
结直肠癌（CRC）仍是全球癌症相关死亡的主要原因，促肿瘤炎症在其发生和发展中起关键作用。慢性炎症是肿瘤发生的主要驱动力和独特机制。尽管先前的研究已经证明了VEGF/p38MAPK和p38MAPK/HSP27信号通路在CRC相关炎症中的重要性，但对整个促肿瘤炎症机制的全面理解仍不完整。
本研究结合网络药理学分析和使用p38MAPK通路抑制剂的药效学实验，系统地鉴定和验证VEGF/p38MAPK/HSP27促肿瘤炎症信号通路。采用蛋白质免疫印迹法确认关键靶蛋白。进行分子对接和微量热泳动（MST）实验，从[植物名称]（PV）中筛选活性化合物。分子动力学（MD）模拟评估化合物-靶点相互作用的稳定性和类药性。
关键蛋白VEGF、p38MAPK和HSP27被确定为信号通路的关键组成部分。发现三种活性化合物芦丁、山奈酚-3-O-芸香糖苷和4,5-二咖啡酰奎宁酸（4,5-Dicqa）与这些靶点具有高亲和力结合。MD模拟支持了这些相互作用的稳定性及其作为候选药物的潜力。
本研究为CRC中促肿瘤炎症相关的药理靶点提供了理论和实验证据。这些发现为开发针对VEGF/p38MAPK/HSP27信号通路的新型抗炎疗法提供了有价值的见解。
