基于网络药理学和实验验证的吴茱萸-干姜治疗胃癌的机制研究
Mechanisms of Zanthoxyli Pericarpium-Zingiberis Rhizoma in the Treatment of Gastric Cancer Based on Network Pharmacology and Experimental Validation.
作者信息
Gu Qian, Duan Shuai, Tibenda Joanna Japhet, Gou Boyun, Huang Shicong, Chen Guoqing, Ning Na, Du Yuhua, Liu Wenjing, Nan Yi, Yuan Ling
机构信息
College of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia, People's Republic of China.
Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia, People's Republic of China.
出版信息
Drug Des Devel Ther. 2025 May 30;19:4537-4566. doi: 10.2147/DDDT.S503874. eCollection 2025.
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.
背景
恶性肿瘤作为全球公共卫生领域的一项重大挑战，对人类生命健康构成了重大威胁。尽管传统化疗能够抑制肿瘤生长，但它常常伴有严重的不良反应和耐受性。在此背景下，中医疗法逐渐获得了广泛认可，并且在胃癌（GC）治疗中发挥着重要作用。作为传统方剂“大建中汤”的核心配伍，花椒与干姜药对（ZP-ZR）在肿瘤治疗中展现出了独特优势。
目的
运用网络药理学、生物信息学分析及体外实验验证，探究ZP-ZR治疗GC的作用机制，为后续实验研究提供理论依据。
患者与方法
随后，通过CCK-8、凋亡、周期及集落形成实验验证ZP-ZR对胃癌HGC-27和AGS细胞系增殖能力的影响。通过伤口愈合、transwell细胞侵袭及transwell细胞迁移实验评估ZP-ZR对GC细胞转移能力的影响。此外，我们通过蛋白质免疫印迹法和qRT-PCR评估枢纽基因、信号通路蛋白及mRNA的表达。
结果
ZP-ZR主要通过调控GC中的表皮生长因子受体（EGFR）、环氧化酶-2（PTGS2）、基质金属蛋白酶-9（MMP9）、趋化因子（CXCL8）、凋亡蛋白（BCL2L1）、细胞周期蛋白依赖性激酶6（CDK6）、原癌基因c-Kit（KIT）靶基因及磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）信号通路来治疗胃癌。ZP-ZR抑制AGS和HGC-27细胞系的增殖、诱导凋亡、阻断细胞周期，并抑制细胞迁移和侵袭。此外，ZP-ZR影响PI3K-Akt相关蛋白的表达，并降低枢纽基因的mRNA表达。
结论
ZP-ZR通过PI3K-Akt信号通路治疗GC。本研究为进一步研究ZP-ZR治疗GC提供了新思路。
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