Particulate matter-induced lung cancer metastasis is inhibited by ginsenoside Rg3

The risk of exposure to particulate matter (PM) has been consistently highlighted globally owing to its detrimental effects on the respiratory and cardiovascular systems and in the development of lung cancer. Additionally, PM promotes cancer cell metastasis; however, research elucidating the precise mechanisms underlying this phenomenon and the strategies to inhibit it remains limited. The aim of this study was to elucidate the mechanism underlying PM-induced cancer metastasis and investigate the preventive role of ginsenoside Rg3. We treated macrophages with PM and confirmed an increase in the expression and secretion of chemokines, such as CCL3, CCL4, and CCL5. This effect was mediated by the MAPK and NF-kB pathways, and Rg3 inhibited this process by suppressing chemokine expression. These chemokines regulate the expression of epithelial-mesenchymal transition (EMT) markers in cancer cells, including Snail, Slug, ZEB1, and E-cadherin. The regulated EMT markers increased the motility of cancer cells in vitro. Furthermore, an increase in CCL3, CCL4, and CCL5 in the bronchoalveolar lavage fluid (BALF) was confirmed in a PM inhalation mouse model, and Rg3 reduced PM-induced cancer metastasis. The study findings suggest the potential use of Rg3 as a therapeutic agent to prevent PM-induced cancer metastasis. (c) 2025 The Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V.