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.