Abstract: OBJECTIVE: To investigate the therapeutic effects of Jiazhu decoction(JZD) in combination with cyclophosphamide(CTX) on the growth of breast cancer in mice and to explore the possible molecular mechanisms of action.METHODS: BALB/c mice were randomly divided into four groups of 10(untreated model group, JZD group, CTX group, and JZD + CTX group) and subcutaneously injected with 4 T1 mouse breast cancer cells.Tumors were allowed to establish for ～7 d before initiation of treatment with CTX(100 mg/kg every week by intraperitoneal injection) and/or JZD(0.015 mL of 1.65 g/mL crude drug, administered daily by gavage).The model group received equivalent volumes of vehicle on the same schedules.Tumor volumes were measured every 3 d.Mice were sacrificed after 3 weeks of treatment, and tumors were excised and subjected to RT-qPCR and western blot analysis to evaluate expression of the Wnt/β-catenin signaling pathway components β-catenin, c-Myc, and cyclin D1 at the mRNA and protein levels.RESULTS: The mean tumor volume was smaller and the growth rate was slower in the CTX and JZD+ CTX groups compared with the model group(P < 0.05), and in the JZD + CTX group compared with the CTX and JZD groups(P < 0.05).Tumor growth was inhibited by 35.4% and 48.1% by CTX and JZD + CTX treatment, respectively(P < 0.001).The expression of β-catenin, c-Myc, and cyclin D1 mRNA and protein in tumors was significantly lower in mice treated with JZD or JZD + CTX compared with the untreated mice(P < 0.05), and was significantly lower in mice treated with JZD + CTX compared with either JZD or CTX alone(P < 0.05).CONCLUSION: JZD inhibited the growth of mouse breast cancer cells in vivo, possibly by reducing the expression of β-catenin, c-Myc, and cyclin D1.Combination therapy with JZD plus CTX had a more potent inhibitory effect on breast cancer growth compared with either agent alone.

Key words: Breast neoplasms, Cyclophosphamide, Wnt signaling pathway, Jiazhu decoction