Maimendong decoction inhibits lung cancer metastasis by increasing the proportion and killing activity of NK cells

Ethnopharmacological relevance: In China, Maimendong Decoction (MMDD) is a classic Chinese medicine prescription for treating lung diseases, such as cough, upper respiratory tract infection, bronchitis, asthma, pulmonary fibrosis and so on. However, the mechanism by which MMDD inhibits lung cancer metastasis remains unclear. Aim of the study: This study seeks to examine the effect of MMDD on suppressing lung cancer metastasis and to uncover its mechanism through the regulation of tumor immunity. Materials and methods: The impact of MMDD on lung cancer cell growth and metastasis was assessed via cell apoptosis, proliferation, and migration assays, alongside lung metastasis models in mice. Hematoxylin-eosin (H&E) staining, immunohistochemistry, and immunofluorescence were used to examine the tissue morphology of metastatic tumors, Ki-67 protein expression, and NK cell infiltration. The potential anti-lung cancer mechanism of MMDD was explored through network pharmacology. Immune cell levels and NK cell function in mouse peripheral blood were analyzed using flow cytometry. Additionally, co-culture and lactate dehydrogenase (LDH) assays were performed to assess NK cell cytotoxicity. Results: MMDD significantly reduced the number of metastatic tumors and the neoplastic burden in the lungs of mice. While MMDD did not affect the proliferation, apoptosis, or migration of lung cancer cells at 1 mg/ml concentration in vitro, it substantially increased NK cell proportion in peripheral blood and metastatic tumor tissues. Moreover, MMDD significantly boosted NK cell cytotoxicity and enhanced their killing effect on lung cancer cells. Importantly, depletion of NK cells abolished the survival-prolonging effect of MMDD in mice. Conclusion: This study demonstrates that MMDD restrains lung cancer cell metastasis primarily by increasing NK cell levels and enhancing their cytotoxic activity. These results offer experimental support for the use of MMDD in treating lung cancer metastasis.