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.
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Authors | Yiyi Ye, Lixia Pei, Jing Ding, Chunyu Wu, Chenping Sun, Sheng Liu |
Journal | International immunopharmacology
(Int Immunopharmacol)
Vol. 67
Pg. 239-247
(Feb 2019)
ISSN: 1878-1705 [Electronic] Netherlands |
PMID | 30562685
(Publication Type: Journal Article)
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Copyright | Copyright © 2018 Elsevier B.V. All rights reserved. |
Chemical References |
- Calgranulin A
- Calgranulin B
- Cytokines
- S100A9 protein, mouse
- S100a8 protein, mouse
- Saponins
- Triterpenes
- platycodin D
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Topics |
- Animals
- Calgranulin A
(administration & dosage)
- Calgranulin B
(toxicity)
- Cell Line, Tumor
- Cell Movement
(drug effects)
- Cell Survival
(drug effects)
- Cytokines
(genetics, metabolism)
- Female
- Gene Expression Regulation
(drug effects)
- Mammary Neoplasms, Animal
(metabolism)
- Mice
- Mice, Inbred BALB C
- Molecular Structure
- Neoplasms, Experimental
(drug therapy, metabolism)
- Saponins
(chemistry, pharmacology)
- Triterpenes
(chemistry, pharmacology)
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