ABSTRACT
OBJECTIVE: To observe the intervention effect of Shugan Jianpi Formula (, SGJPF) on a breast cancer mouse model with depression and investigate the underlying mechanism of SGJPF in preventing the development of breast cancer. METHODS: The breast cancer model was induced by inoculation of breast cancer cells, the depression model was induced by chronic stress stimuli, and the depression cancer model was established by combining the two factors. The mice were divided into 7 groups: normal control, depression model, tumor model, depression tumor model, SGJPF, chemotherapy, and SGJPF+chemotherapy groups. The last 3 groups were depression breast cancer mice and treated respectively with SGJPF, chemotherapy drug gemcitabine (GEM), and SGJPF alongside GEM. The condition of the mice was evaluated by the expression of 5-hydroxytryptamine in hippocampus after the sucrose water test and open field test, weight change, and survival time. Tumor growth was monitored with in vivo imaging. Flow cytometry was used to analyze the level of myeloid-derived suppression cell (MDSC) in the mouse spleen, T cell subsets, and the early apoptosis of CD8+ T cells. RESULTS: The SGJPF+GEM group had the highest inhibition rate and the longest survival time (P<0.01). The MDSC level and the apoptosis rate of CD8+ T cells was the highest in the SGJPF+GEM group (P<0.05). CONCLUSIONS: Depressive disorders and tumor growth could suppress the immune function of mice to different degrees, and the microenvironment in late 4T1 inflammatory breast cancer may play an important role in the pathological process. SGJYF could regulate the immune microenvironment by reducing CD8+ T lymphocyte apoptosis and tumor cell activity, increasing immune surveillance capability, and inhibiting MDSC proliferation, thus prolonging the survival time of tumor-bearing mice.
Subject(s)
Depression/complications , Depression/drug therapy , Drugs, Chinese Herbal/therapeutic use , Mammary Neoplasms, Animal/complications , Mammary Neoplasms, Animal/drug therapy , Myeloid-Derived Suppressor Cells/pathology , Animals , Apoptosis/drug effects , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Female , Hippocampus/metabolism , Mammary Neoplasms, Animal/immunology , Mice, Inbred BALB C , Serotonin/metabolism , Spleen/pathology , Survival Analysis , T-Lymphocyte Subsets/drug effects , Tumor Burden/drug effectsABSTRACT
<p><b>OBJECTIVE</b>To observe the intervention effect of Shugan Jianpi Formula (, SGJPF) on a breast cancer mouse model with depression and investigate the underlying mechanism of SGJPF in preventing the development of breast cancer.</p><p><b>METHODS</b>The breast cancer model was induced by inoculation of breast cancer cells, the depression model was induced by chronic stress stimuli, and the depression cancer model was established by combining the two factors. The mice were divided into 7 groups: normal control, depression model, tumor model, depression tumor model, SGJPF, chemotherapy, and SGJPF+chemotherapy groups. The last 3 groups were depression breast cancer mice and treated respectively with SGJPF, chemotherapy drug gemcitabine (GEM), and SGJPF alongside GEM. The condition of the mice was evaluated by the expression of 5-hydroxytryptamine in hippocampus after the sucrose water test and open field test, weight change, and survival time. Tumor growth was monitored with in vivo imaging. Flow cytometry was used to analyze the level of myeloid-derived suppression cell (MDSC) in the mouse spleen, T cell subsets, and the early apoptosis of CD8T cells.</p><p><b>RESULTS</b>The SGJPF+GEM group had the highest inhibition rate and the longest survival time (P<0.01). The MDSC level and the apoptosis rate of CD8T cells was the highest in the SGJPF+GEM group (P<0.05).</p><p><b>CONCLUSIONS</b>Depressive disorders and tumor growth could suppress the immune function of mice to different degrees, and the microenvironment in late 4T1 inflammatory breast cancer may play an important role in the pathological process. SGJYF could regulate the immune microenvironment by reducing CD8T lymphocyte apoptosis and tumor cell activity, increasing immune surveillance capability, and inhibiting MDSC proliferation, thus prolonging the survival time of tumor-bearing mice.</p>
