APPLICATION OF SMS2 INHIBITOR IN PREPARATION OF DRUG FOR TREATMENT OF HIGHLY INVASIVE BREAST CANCER

摘要

An application of an SMS2 inhibitor in the preparation of a drug for the treatment of highly invasive breast cancer. According to overall experiments using 4T1 cells to establish a mouse triple-negative breast cancer model and in vitro experiments using primary bone marrow macrophages from mice, it is confirmed that compound I, as an SMS2 specific inhibitor, is able to effectively inhibit type 2 polarization of macrophages by decreasing sphingomyelin synthase 2 activity and sphingolipid levels in vivo, and is able to remold a tumor microenvironment by reducing M2-type macrophages in the tumor microenvironment of triple-negative breast cancer and by reducing the extent of infiltration of other myeloid-derived immunosuppressive cells, thereby inhibiting the in situ growth of the triple-negative breast cancer as well as the formation and growth of pulmonary metastases brought about through blood circulation. Inhibition of SMS2 activity may be used to prevent and treat highly invasive malignant breast cancers comprising triple-negative breast cancer.