Ginseng extract (Ginsenoside RG3) combined with STING agonist reverses TAM/M2 polarization to inhibit TNBC evolution

This study aims to investigate the enhanced anti-tumor effects and potential mechanisms of the combination of ginsenoside Rg3 with STING agonist through in vitro and in vivo experiments. In vitro experiments were conducted using MDA-MB-231 and Hs578T TNBC cells. Multiple techniques, including Western blotting, MTT assays, colony formation assays, wound healing assays, Transwell assays, immunofluorescence (IF), flow cytometry, and endothelial tube formation assays, were used to assess the effects and mechanisms of Rg3 and the STING agonists. In addition, a mouse xenograft model was established and validated in vivo, using immunohistochemistry and other detection methods. In vitro experiments showed that the combination of ginsenoside Rg3 and the STING agonist significantly inhibited the proliferation TNBC cells, suppressed TNBC cell stemness and the EMT process, and promoted apoptosis in TNBC cells. Moreover, their combined use altered the tumor microenvironment by inducing TAM/M1 polarization and reversing TAM/M2 polarization. It is worth noting that ginsenoside Rg3 inhibited the activation of NF-κB during the anti-tumor process of STING agonists, effectively impeding the growth, migration, and invasion of TNBC. In vivo experiments also corroborated these findings. The combination of ginsenoside Rg3 and STING agonist exerts superior anti-tumor effects by altering the biological functions of tumor cells and modifying the tumor microenvironment. This combination method provides a new treatment strategy for clinical treatment. • Effects on tumour cells: This study investigates the effects of RG3 combined with STING agonists on tumour cell function. • Effects on Tumor Microenvironment: RG3 and STING agonists alter macrophages and cytokines in the TME. • Mechanism with RG3 and STING Agonists: How the combination inhibits the evolution of TNBC and its mechanisms. • Novel Treatment Approach: First combination in cancer treatment aims to improve efficacy and reduce side effects.