Therapeutic Effect of Gemcitabine Combined With Angelica Polysaccharide on Triple Negative Breast Cancer in Mice.

OBJECTIVE: This study delves into the therapeutic effects of combining GEM and Angelica polysaccharide (APS) on triple-negative breast cancer. METHODS: In vitro, proliferation, apoptosis of 4T-1 cells and MDSC were detected by flow cytometry. Migration of 4T-1 cell was detected by scratch healing experiment after treatment by GEM (0, 2.5, 5 μM), APS (160,320 mg/ml), or GEM + APS (2.5 μM + 160 mg/ml, 5 μM + 320 mg/ml). In vivo, 4T-1 cells were injected into the mammary fat pad under the mammary gland of BALB/c mice to establish an orthotopic breast cancer tumor model. They were randomly divided into control group (0.9% normal saline + ultrapure water), GEM group (0.9% normal saline preparation, 100 mg/kg, intraperitoneal injection twice a week), APS group (ultrapure water preparation, 200 mg/kg, intraperitoneal injection once a day), GEM + APS group (GEM 100 mg/kg, intraperitoneal injection twice a week and APS 200 mg/kg, intraperitoneal injection once a day) for 3 weeks. The proportion of immune cells in the spleen and tumor microenvironment were detected by flow cytometry, immunofluorescence and Mindray hematology analyzer. The tumor volume and weight, spleen index were recorded. RESULTS: The in vitro experimental results revealed that GEM effectively inhibited the proliferation and migration of 4T-1 cells and induced apoptosis in both 4T-1 cells and MDSCs. In contrast, APS had no impact on 4T-1 cells or MDSCs. The in vivo experimental findings indicated that compared with the single-drug treatment groups, the combination treatment of GEM + APS more effectively regulated the proportion of peripheral and local anti-tumor MDSCs and T cells, and more significantly curbed the progression of breast cancer in mice. CONCLUSION: APS can exert a synergistic effect through immune regulation to enhance the therapeutic efficacy of GEM on triple-negative breast cancer. It aims to offer novel insights for the clinical application of combining GEM with immunotherapy for patients with triple negative breast cancer.