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

Metastasis is the leading cause of cancer-related deaths worldwide. The circulating tumor cells (CTCs) are essential targets for the prevention and treatment of metastasis. Traditional Chinese medicine treatment may achieve the effect of preventing lung cancer metastasis by intervening in CTC during long-term medication. Tiao-Shen-Zhi-Ai Formular (TSZAF) is a Chinese medicine compound prescription used in clinical practice for the treatment of lung cancer. In this study, we selected three main effective and active ingredients from the TSZAF and combined them into a new TSZAF monomer combination (TSZAF mc) to study its effect and mechanism in inhibiting lung cancer metastasis. TSZAF mc significantly inhibited the proliferation, migration and invasion of CTC-TJH-01 and LLC cells, and induced apoptosis of the cells in vitro. Additionally, TSZAF mc also significantly inhibited the growth and metastasis of LLC cells in vivo. Mechanistically, TAZSF mc significantly inhibited the Wnt/β-catenin signaling pathway and the expression of CXCL5 in lung cancer cells and tissues. Furthermore, TAZSF mc significantly downregulated the infiltration level of neutrophils in metastatic lesions. These results suggest that TSZAF mc inhibits the growth and metastasis of lung cancer by down-regulating the Wnt/β-catenin signaling pathway, and decreasing CXCL5 secretion to reduce the recruitment and infiltration of neutrophils. TSZAF mc has the potential to be an effective therapeutic agent against lung cancer metastasis.