Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Zhang Heng Road, Pudong New Area, Shanghai 201203, China.
Department of Oncology, Chinese Medicine Hospital of Wujin, Changzhou 213100, China.
Curr Pharm Des. 2024;30(9):683-701. doi: 10.2174/0113816128287232240213105913.
Recent studies have shown that XihuangWan (XHW) is a kind of Chinese medicine with significant anti-tumor and anti-inflammatory activities. However, its mechanism for preventing and treating radiation proctitis in rectal cancer patients during radiotherapy remains unclear.
This study employed the network pharmacology to establish a "drug-active ingredient-target genedisease" network via using TCMSP, SymMap, GeneCard, and OMIM databases. The PPI network was conducted by the String tool. The core targets of XHW in the treatment of rectal cancer and radiation enteritis were identified by topological analysis, and the functional annotation analysis and pathway enrichment analysis were performed.
A total of 61 active ingredients of XHW ingredients, 4607 rectal cancer-related genes, 5803 radiation enteritis-related genes, and 68 common targets of XHW in the treatment of rectal cancer and radiation enteritis were obtained. PTGS1 and NR3C2, as identified potential targets, were significantly associated with OS of colorectal cancer patients. GO and KEGG enrichment analysis showed that bioinformatics annotation of these common genes was mainly involved in DNA-binding transcription factor, PI3K/Akt, TNF, HIF-1 signaling pathway, and colorectal cancer pathway.
The active ingredients of XHW, mainly including Quercetin, Ellagic acid, and Stigmasterol, might act on common targets of rectal cancer and radiation enteritis, such as PTGS1, NR3C2, IL-6, EGFR, HIF-1A, CASP3, BCL2, ESR1, MYC, and PPARG, and regulate multiple signaling pathways like PI3K-Akt, TNF, and HIF-1 to inhibit tumor proliferation, tumor angiogenesis, inflammatory responses, and oxidative stress, thereby achieving prevention and treatment of radiation enteritis in rectal cancer patients during radiotherapy. It provided an important reference for further elucidating the anti-inflammation and anti-tumor mechanism and clinical application of XHW.
最近的研究表明，西黄丸（XHW）是一种具有显著抗肿瘤和抗炎活性的中药。然而，其在直肠癌患者放疗期间预防和治疗放射性直肠炎的机制尚不清楚。
本研究采用网络药理学，通过 TCMSP、SymMap、GeneCard 和 OMIM 数据库构建“药物-活性成分-靶基因-疾病”网络。利用 String 工具构建 PPI 网络。通过拓扑分析确定 XHW 治疗直肠癌和放射性肠炎的核心靶点，并进行功能注释分析和通路富集分析。
共获得 XHW 成分的 61 种活性成分、4607 个直肠癌相关基因、5803 个放射性肠炎相关基因和 XHW 治疗直肠癌和放射性肠炎的 68 个共同靶点。PTGS1 和 NR3C2 作为潜在靶点，与结直肠癌患者的 OS 显著相关。GO 和 KEGG 富集分析表明，这些共同基因的生物信息学注释主要涉及 DNA 结合转录因子、PI3K/Akt、TNF、HIF-1 信号通路和结直肠癌通路。
XHW 的活性成分主要包括槲皮素、鞣花酸和豆甾醇等，可能通过作用于直肠癌和放射性肠炎的共同靶点，如 PTGS1、NR3C2、IL-6、EGFR、HIF-1A、CASP3、BCL2、ESR1、MYC 和 PPARG，调节 PI3K-Akt、TNF、HIF-1 等多种信号通路，抑制肿瘤增殖、肿瘤血管生成、炎症反应和氧化应激，从而达到预防和治疗直肠癌患者放疗期间放射性肠炎的目的。为进一步阐明 XHW 的抗炎和抗肿瘤机制及临床应用提供了重要参考。
