Abstract
Ginsenoside Rg3 (Rg3) has been studied in several cancer models and is suggested to act through various pharmacological effects. We investigated the anticancer properties of Rg3 through myeloid-derived suppressor cell (MDSC) modulation in FM3A mouse mammary carcinoma cells. The effects of Rg3 on MDSCs and consequent changes in cancer stem-like cells (CSCs) and epithelial-mesenchymal transition (EMT) were evaluated by diverse methods. MDSCs promoted cancer by enhancing breast cancer stemness and promoting EMT. Rg3 at a dose without obvious cytotoxicity downregulated MDSCs and repressed MDSC-induced cancer stemness and EMT. Mechanistic investigations suggested that these inhibitory effects of Rg3 on MDSCs and corresponding cancer progression depend upon suppression of the STAT3-dependent pathway, tumor-derived cytokines, and the NOTCH signaling pathway. In a mouse model, MDSCs accelerated tumor progression, and Rg3 delayed tumor growth, which is consistent with the results of in vitro experiments. These results indicated that Rg3 could effectively inhibit the progression of breast cancer. The anticancer effect of Rg3 might be partially due to its downregulation of MDSCs and consequent repression of cancer stemness and EMT in breast cancer. Hence, we suggest the regulation of MDSCs through Rg3 treatment as an effective therapeutic strategy for breast cancer patients.
Highlights
Breast cancer is one of the most commonly diagnosed female cancers worldwide, and it is estimated that approximately one-third of newly diagnosed cancers in women in 2019 were breast cancer [1]
These results indicated that FM3A breast cancer cells promoted myeloid-derived suppressor cell (MDSC) and that Rg3 had an inhibitory effect on MDSCs
We further found that expression of the cancer stemness-related proteins GLUT1, ALDH1, OCT4, and KLF4 were upregulated in the presence of MDSCs and dose-dependently downregulated after treatment with Rg3 (Fig 2C)
Summary
Breast cancer is one of the most commonly diagnosed female cancers worldwide, and it is estimated that approximately one-third of newly diagnosed cancers in women in 2019 were breast cancer [1]. Objective clinical responses to some chemotherapy regimens are obtainable, most advanced
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