Investigating the Mechanism of Jiawei Weijin Decoction in Treating Non-Small Cell Lung Cancer Using Network Pharmacology, Bioinformatics Analysis and Experimental Validation.

IF 5.1 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-09-25 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S516745

Bo Xu, Yihan Yu, Jixian Zhang, Bo Jiang, Le Yan, Saili Chen, Linling Hu, Qing Miao, Yu Qi

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引用次数: 0

Abstract

Purpose: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide. While Qianjin Weijin Decoction is widely used in China for lung cancer treatment, Jiawei Qianjin Weijin Decoction (JWWJD), a modified version, has shown enhanced anti-metastatic effects. However, its active components and underlying mechanisms remain unclear.

Methods: The effect of JWWJD against NSCLC was evaluated in vitro and in vivo, and the mechanisms were identified in combination with transcriptomics. Network pharmacology and bioinformatics were used to construct an anti-NSCLC prognostic model with JWWJD. The correlation between the expression of the prognostic gene and clinicopathological features was evaluated. The main active components of JWWJD were identified by LC-MS/MS and its anticancer effect and mechanism were investigated in vitro and in vivo.

Results: JWWJD-containing serum significantly suppressed cell proliferation and migration, and induced apoptosis in NCI-A549 and NCI-H23 cells. Among different concentrations tested, 20% drug-containing serum showed the most potent inhibitory effect on NSCLC progression (all P-values < 0.05). In a BALB/c-nu mouse xenograft model, oral administration of high-dose JWWJD reduced tumor volume by 27.76% compared to control (P < 0.001). Transcriptomic analysis revealed that JWWJD treatment led to significant downregulation of SPP1 (Fold Change = 0.687, FDR < 0.05), a gene highly associated with poor prognosis in NSCLC patients. Using LC-MS/MS, curcumol was identified as the key active component in JWWJD. Molecular studies demonstrated that curcumol directly binds to SPP1 with strong affinity (KD = 4.55×10^-6 M), downregulates its expression, and inhibits NSCLC cell migration and invasion. In vivo experiments showed that curcumol reduced tumor volume by 24.88% (P < 0.001).

Conclusion: Our study, integrating transcriptomics, bioinformatics, LC-MS/MS, and experimental validation, revealed that JWWJD alleviates NSCLC metastasis by directly targeting SPP1. JWWJD and its active compound curcumol show promise as alternative therapies for NSCLC patients.

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用网络药理学、生物信息学分析及实验验证探讨加味味金汤治疗非小细胞肺癌的机制。

目的：非小细胞肺癌（NSCLC）是全球癌症相关死亡的主要原因。虽然前进胃金汤在中国被广泛用于治疗肺癌，但加味前进胃金汤（JWWJD）的改良版本显示出增强的抗转移作用。然而，其有效成分和潜在机制尚不清楚。方法：在体外和体内评价JWWJD抗NSCLC的作用，并结合转录组学方法鉴定其作用机制。应用网络药理学和生物信息学方法构建JWWJD抗nsclc预后模型。评估预后基因表达与临床病理特征的相关性。采用LC-MS/MS鉴定了其主要活性成分，并对其体外和体内的抗癌作用及机制进行了研究。结果：含jwwjd血清能明显抑制NCI-A549和NCI-H23细胞的增殖和迁移，诱导细胞凋亡。不同浓度中，20%含药血清对NSCLC进展的抑制作用最强（p值均< 0.05）。在BALB/c-nu小鼠异种移植模型中，与对照组相比，口服高剂量JWWJD可使肿瘤体积减少27.76% （P < 0.001）。转录组学分析显示，JWWJD治疗导致NSCLC患者预后不良相关基因SPP1显著下调（Fold Change = 0.687, FDR < 0.05）。采用LC-MS/MS技术鉴定姜黄酚为其主要活性成分。分子研究表明，姜黄酚直接与SPP1亲和力强（KD = 4.55×10-6 M）结合，下调其表达，抑制NSCLC细胞迁移和侵袭。体内实验显示姜黄酚可使肿瘤体积减小24.88% （P < 0.001）。结论：结合转录组学、生物信息学、LC-MS/MS和实验验证，我们的研究揭示了JWWJD通过直接靶向SPP1缓解NSCLC转移。JWWJD及其活性化合物姜黄酚有望成为非小细胞肺癌患者的替代疗法。

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.