Abstract
Tumor-associated macrophages (TAMs) account for more than 50% of the cells in the tumor immune microenvironment of patients with breast cancer. A high TAM density is associated with a poor clinical prognosis. Targeting TAMs is a promising therapeutic strategy because they promote tumor growth, development, and metastasis. In this study, we found that dimethyl formamide (DMF) significantly inhibited the tumor invasion-promoting ability of TAMs in the co-culture system and further showed that DMF functioned by reducing reactive oxygen species (ROS) production in TAMs. The orthotopic 4T1 cell inoculation model and the spontaneous mouse mammary tumor virus-polyoma middle tumor-antigen tumor model were used to evaluate the antitumor effect of DMF. The results showed that DMF significantly inhibited tumor metastasis and increased T-cell infiltration into the tumor microenvironment. Mechanistically, NRF2 activation was necessary for DMF to exert its function, and DMF can play a role in breast cancer as an anticancer drug targeting TAMs.
Highlights
Breast cancer is a malignant tumor with a high incidence among women worldwide, presenting as a heterogeneous disease
The results showed that dimethyl formamide (DMF) had a significant inhibitory effect on the viability of RAW264.7 macrophages when the concentration was higher than 100 nM (Figures 1A, B)
The results showed that DMF affected the invasion-promoting ability of Tumor-associated Macrophages (TAM)
Summary
Breast cancer is a malignant tumor with a high incidence among women worldwide, presenting as a heterogeneous disease. According to the expression differences of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), breast cancer can be divided into four molecular subtypes. According to the treatment guidelines, endocrine intervention, chemotherapy, and other drugs are used as the first-line treatment for patients with breast cancer in China. Selective estrogen receptor downregulation, aromatase inhibitors, docetaxel, or synergistic drug regimens are mainly used for treatment. These treatment strategies are the most important elements in the comprehensive treatment of patients with breast cancer as they have remarkable curative effects, Abbreviations: DMF, Dimethyl Formamide; ROS, Reactive Oxygen Species; TAM, Tumor-associated Macrophages; MMTVPyMT, Murine Mammary Tumor Virus- Polyoma Middle T Antigen; CON, Control
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