Protective Effect of Traditional Chinese Medicine Formula RP on Lung Microenvironment in Pre-Metastasis Stage of Breast Cancer

Abstract

Background: Inflammatory response and inflammation-induced vascular hyper-permeability were established leading to the abnormalities of the pulmonary microenvironment in pre-metastasis stage of breast cancer. Ruyiping is a commonly used compound drug for clinical treatment of breast cancer metastasis, and Platycodon grandiflorum is mainly used to treat pulmonary inflammatory diseases. Therefore, this study used ruyiping combined with Platycodon grandiflorum (abbreviated as RP) to investigate their inhibitory effect on pre-metastatic microenvironment of lung in 4T1 tumor-bearing mice. Study Design and Methods: The permeability of lung tissue was detected by Evans blue method. The localization of S100A8/A9 in lung tissue was obtained by double-labeling immunofluorescence staining. The level of fibrinogen in pre-metastatic microenvironment of lung as well as the levels of pro-inflammatory factors (interleukin [IL]-1β and IL-6) and chemokines (CXCL2 and CXCL5) in bronchoalveolar lavage fluid was detected by ELISA (enzyme-linked immunosorbent assay). Results: From the experimental results, RP could protect the integrity of microvascular, inhibit the release of S100A8/A9, reduce the extravasation of fibrinogen, and decrease the expressions of IL-1β, IL-6, CXCL2, and CXCL5. Conclusions: RP could inhibit the extravasation of fibrinogen by protecting pulmonary vascular integrity and then interrupted its interaction with carcinoma in situ, thereby inhibiting the formation of inflammatory pre-metastatic microenvironment.