Thalidomide suppresses breast cancer tumor growth by inhibiting tumor-associated macrophage accumulation in breast tumor-bearing mice

Abstract

we aimed to explore the role of thalidomide in breast cancer by using a mouse 4T1 breast tumor model. A tumor model was established by injecting logarithmic-phase 4T1 cells into the mammary fat pat.Tumor growth was monitored every day and tumor size was measured periodically. Which were performed to determine the cytokine and related gene mRNA expression, the cytokine production and protein expression, check the vessel formation and necrosis, the CD31 expression,the expression of CD31, F4/80 and CD206,staining the digested cells with F4/80, cd45 and CD11b to determine the M2 type macrophages accumulation by qRT-PCR, Cytokine antibody array, HE staining, Immunohistochemistry, Immunostaining, Flow cytometry, respectively. In the current study, Our results indicated that thalidomide significantly inhibited tumor growth in the mouse model by inhibiting angiogenesis and promoting the necrosis of tumor cells in tumor tissues.Moreover, immunostaining and flow cytometry results demonstrated that M2-type tumor-associated macrophage accumulation and infiltration were profoundly inhibited upon treatment with thalidomide. In addition, thalidomide treatment also regulated cytokine production by inhibiting the production of angiogenesis-related cytokines, such as G-CSF, VEGF-B, VEGFR1, VEGFR3 and IL-10. In conclusion, our studies explored the antitumor effect of thalidomide in a breast tumor model and uncovered that thalidomide inhibited breast tumor growth by inhibiting angiogenesis as a result of reducing TAM accumulation and infiltration and inhibiting angiogenesis-related cytokine production.