Sophoraflavanone G decreases the migratory ability of cancer cells by altering the cytokine profile of the environment in endometrial cancer and macrophage co-culture

Abstract

Background : Macrophages play key roles in initiating, sustaining, and resolving inflammation. Sophora flavescens has traditionally been used as a herbal anti-inflammatory treatment for inflammation-related conditions. This study aimed to investigate how sophoraflavanone G (SF-G) modulates the inflammatory response in RAW264.7 macrophages when co-cultured with Ishikawa endometrial cancer cells. Methods : The cytotoxicity of SF-G in RAW264.7 cells was assessed using the Cell Counting Kit-8 (CCK-8) assay. Gene expression analyses of inflammatory markers in macrophages and migration-related genes in co-cultured endometrial cancer cells were performed using quantitative Real-time Polymerase Chain Reaction (qRT-PCR). Protein levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA). Unstimulated RAW264.7 cells were used as the control group. Results : Co-culture with cancer cells significantly increased the expression of pro-inflammatory genes (Interleukin 1 beta ( IL1 β ), Interleukin 6 ( IL6 ), Cluster of Differentiation 86 ( CD86 ), and Transforming Growth Factor beta ( TGF β )) in macrophages. Treatment of macrophages with SF-G significantly upregulated anti-inflammatory markers (Cluster of Differentiation 163 ( CD163 ) and Interleukin 10 ( IL10 )) during co-culture with cancer cells. Furthermore, the migratory ability of Ishikawa cells was markedly reduced in the co-culture with SF-G-treated macrophages compared with the co-culture without SF-G. Conclusions : Overall, SF-G treatment altered the inflammatory response of RAW264.7 macrophages in the co-culture microenvironment and inhibited the migration of Ishikawa endometrial cancer cells.