Abstract

Activation of the inflammatory signaling pathway is the most vital part of the pre-metastatic events of breast cancer. Platycodin D (PlaD) shows favorable pharmacological activities in anti-inflammatory and anti-tumor effect. The main purpose of this study was to survey the effects of PlaD on S100A8/A9-induced inflammation in mouse mammary carcinoma 4T1 cells. S100A8/A9 immunolocalization and expression in pre-metastatic lung tissue were assessed by immunofluorescence staining and ELISA . 4T1 cells were treated with 2.5 μg/mL recombinant S100A8/A9 heterodimer and 7.5, 10, or 12.5 μM of PlaD. After 24 h of incubation, cell viability , migration, and invasion were evaluated by CCK-8, wound-healing, and transwell assay, respectively. Nuclear translocation of NF-κB p65 was determined by immunostaining and western blot . The levels of pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α were detected by ELISA. The results showed that S100A8/A9 was actively increased and released into the extracellular space during the pre-metastatic phase of breast cancer. PlaD treatment attenuated S100A8/A9-induced growth, migration, and invasion of 4T1 cells. Furthermore, PlaD decreased the levels of IL-1β, IL-6, and TNF-α by inhibiting nuclear translocation of NF-κB p65. In conclusion, this study demonstrated that PlaD inhibited S100A8/A9-induced inflammatory response in 4T1 cells by suppressing the expression of IL-6, IL-1β, and TNF-α via inhibition of NF-κB signaling pathways.