Abstract Context Xiaoyaosan (XYS), a traditional Chinese medicine (TCM), has been widely used to relieve a variety of disorders caused by depression. Objective This study evaluates the effect of XYS against tumour metastasis in a chronic restraint stress mouse model. Methods and materials Forty C57BL/6J mice were randomly divided into four groups, including blank-control (BC), blank-stress (BS), XYS-control (XC) and XYS-stress (XS). BS and XS groups were exposed to immobilization stress for 2 h per day for 28 days commencing seven days before tumour cell injection. XC and XS groups were given a gavage of XYS (1516.67 mg/kg) before chronic immobilization stress. Mice were injected with HT-29 colon cancer cells in the spleen to produce liver metastasis. After 28 days of injecting with HT-29 cells, flow cytometry, western blot, PCR and immunohistochemical staining were performed to uncover the role of chronic restraint stress and XYS in the liver metastasis of colon cancer. Results Metastatic liver weight of mice in XS group (3.33 ± 0.18 g) was significantly lower than BS group (4.01 ± 0.27 g). Chronic restraint stress significantly increased CD11b+F4/80+ and CD11b+GrloLy6Chi cell infiltration. XYS treatment significantly decreased the CD11b+F4/80+ tumour-associated macrophage (TAM) population and CD11b+GrloLy6Chi myeloid-derived suppressor cell (MDSC). TGF-β, IL-6, MMP-9 and VEGF in spleen tumours significantly decreased in XYS group. XYS also reduced VEGF and CD31 in hepatic metastatic tissue, which were elevated by chronic restraint stress. Conclusions XYS may successfully inhibit chronic-stress-induced liver metastasis. Results suggest that XYS may have therapeutic value for colorectal cancer treatment.

中文翻译：

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中药逍遥散在体内抑制慢性束缚应激诱导的结肠癌肝转移

摘要 背景 逍遥散（XYS）是一种中药，已被广泛用于缓解抑郁症引起的各种疾病。目的 本研究在慢性束缚应激小鼠模型中评估 XYS 对肿瘤转移的影响。方法与材料 40只C57BL/6J小鼠随机分为4组，分别为空白对照（BC）、空白应激（BS）、XYS对照（XC）和XYS应激（XS）。从注射肿瘤细胞前 7 天开始，BS 和 XS 组暴露于固定应力下，每天 2 小时，持续 28 天。XC 和 XS 组在慢性固定应激前灌胃 XYS (1516.67 mg/kg)。在小鼠脾脏中注射HT-29结肠癌细胞以产生肝转移。注射 HT-29 细胞 28 天后，流式细胞术，蛋白质印迹，进行PCR和免疫组织化学染色以揭示慢性束缚应激和XYS在结肠癌肝转移中的作用。结果 XS组小鼠转移肝重量（3.33±0.18g）显着低于BS组（4.01±0.27g）。慢性束缚应激显着增加 CD11b+F4/80+ 和 CD11b+GrloLy6Chi 细胞浸润。XYS 治疗显着降低了 CD11b+F4/80+ 肿瘤相关巨噬细胞 (TAM) 群体和 CD11b+GrloLy6Chi 髓源性抑制细胞 (MDSC)。XYS组脾肿瘤中TGF-β、IL-6、MMP-9和VEGF显着降低。XYS 还降低了肝转移组织中的 VEGF 和 CD31，它们因慢性束缚应激而升高。结论 XYS可成功抑制慢性应激性肝转移。