TSZAF monomer combination downregulates the Wnt/β-catenin signaling pathway and inhibits neutrophil recruitment to prevent lung cancer metastasis

IF 4.9 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines Pub Date : 2025-09-01 DOI:10.1016/S1875-5364(25)60973-3

Pan Yu , Jialiang Yao , Long Zhang , Yanhong Wang , Xinyi Lu , Jiajun Liu , Zujun Que , Yao Liu , Qian Ba , Jiwei Liu , Yan Wu , Jianhui Tian

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引用次数: 0

Abstract

Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.

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TSZAF单体联合下调Wnt/β-catenin信号通路，抑制中性粒细胞募集，预防肺癌转移

转移仍然是世界范围内癌症相关死亡的主要原因。循环肿瘤细胞（CTCs）是预防和治疗转移的关键靶点。中药可能通过长期干预CTC活性来预防肺癌转移。调参止爱方（TSZAF）是临床上用于治疗肺癌的中药复方。本研究将TSZAF的三种主要活性成分组合成一种新的TSZAF单体组合（TSZAF mc），研究其抗转移作用及其机制。TSZAF mc在体外对CTC-TJH-01和LLC细胞具有明显的增殖、迁移和侵袭抑制作用，同时诱导细胞凋亡。此外，TSZAF mc在体内显著抑制LLC细胞的生长和转移。在机制上，TAZSF mc显著抑制肺癌细胞和组织中Wnt/β-catenin信号通路和CXCL5的表达。此外，TAZSF可显著减少转移性病变中的中性粒细胞浸润。这些发现表明，TSZAF mc通过抑制Wnt/β-catenin信号通路，减少CXCL5分泌，从而减少中性粒细胞的募集和浸润，从而抑制肺癌的生长和转移。tszafmc作为一种治疗肺癌转移的有效药物，具有一定的潜力。

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来源期刊

Chinese Journal of Natural Medicines INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY

CiteScore

7.50

自引率

4.30%

发文量

2235

期刊介绍： The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM). Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.