Mechanisms of Zanthoxyli Pericarpium-Zingiberis Rhizoma in the Treatment of Gastric Cancer Based on Network Pharmacology and Experimental Validation.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-05-30 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S503874

Qian Gu, Shuai Duan, Joanna Japhet Tibenda, Boyun Gou, Shicong Huang, Guoqing Chen, Na Ning, Yuhua Du, Wenjing Liu, Yi Nan, Ling Yuan

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引用次数: 0

Abstract

Background: Malignant tumors, as a major challenge in global public health, have posed a significant threat to human life and health. Although traditional chemotherapy can inhibit tumor growth, it is often associated with serious adverse effects and tolerance. Against this background, Chinese medicine therapies have gradually gained wide recognition, and they play an important role in the treatment of gastric cancer (GC). As the core combination of the traditional prescription "Dajianzhong Tang", the medicinal pair of Zanthoxyli Pericarpium and Zingiberis Rhizoma (ZP-ZR) has shown unique advantages in tumor treatment.

Purpose: To explore the mechanism of action of ZP-ZR in the treatment of GC using network pharmacology, bioinformatics analysis and in vitro experimental validation, and to provide a theoretical basis for subsequent experimental studies.

Patients and methods: Subsequently, the effects of ZP-ZR on the proliferative ability of gastric cancer HGC-27 and AGS cell lines were verified by CCK-8, apoptosis, cycle and colony formation assays. The effects of ZP-ZR on the metastatic ability of GC cells were evaluated by Wound healing, transwell cell invasion and transwell cell migration assays. In addition, we evaluated the expression of Hub genes, pathway proteins and mRNAs by Western blot and qRT-PCR.

Results: ZP-ZR mainly regulated EGFR, PTGS2, MMP9, CXCL8, BCL2L1, CDK6, KIT target genes and PI3K/Akt pathway in GC for the treatment of gastric cancer. ZP-ZR inhibited the proliferation, induced apoptosis, blocked the cell cycle, and inhibited cell migration and invasion in AGS and HGC-27 cell lines. In addition, ZP-ZR affected the expression of PI3K-Akt-related proteins and decreased the mRNA expression of Hub genes.

Conclusion: ZP-ZR treats GC through the PI3K-Akt pathway.The present study provides a new idea for further investigation of ZP-ZR in the treatment of GC.

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基于网络药理学及实验验证的花椒皮姜治疗胃癌的作用机制。

背景：恶性肿瘤是全球公共卫生面临的重大挑战，对人类生命和健康构成重大威胁。传统化疗虽能抑制肿瘤生长，但往往伴有严重的不良反应和耐受性。在此背景下，中医药疗法逐渐得到广泛认可，在胃癌的治疗中发挥着重要作用。作为传统方剂“大建中汤”的核心组合，花椒皮与姜黄（ZP-ZR）药用对在肿瘤治疗中表现出独特的优势。目的：通过网络药理学、生物信息学分析和体外实验验证，探讨ZP-ZR治疗GC的作用机制，为后续实验研究提供理论基础。患者和方法：随后，通过CCK-8、凋亡、周期和集落形成实验验证ZP-ZR对胃癌HGC-27和AGS细胞株增殖能力的影响。通过伤口愈合、transwell细胞侵袭和transwell细胞迁移实验评估ZP-ZR对胃癌细胞转移能力的影响。此外，我们通过Western blot和qRT-PCR检测Hub基因、通路蛋白和mrna的表达。结果：ZP-ZR主要调控胃癌中EGFR、PTGS2、MMP9、CXCL8、BCL2L1、CDK6、KIT靶基因及PI3K/Akt通路，治疗胃癌。ZP-ZR对AGS和HGC-27细胞株具有抑制增殖、诱导凋亡、阻断细胞周期、抑制细胞迁移和侵袭的作用。ZP-ZR影响pi3k - akt相关蛋白的表达，降低Hub基因mRNA的表达。结论：ZP-ZR通过PI3K-Akt通路治疗GC。本研究为进一步研究ZP-ZR在气相色谱处理中的作用提供了新的思路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.