Anti-angiogenic activity of ShengMaBieJia decoction in vitro and in acute myeloid leukaemia tumour-bearing mouse models

CONTEXT: ShengMaBieJia decoction (SMBJD) is used to treat solid and hematological tumours; however, its anti-angiogenesis activity remains unclear. OBJECTIVE: This study verified the anti-angiogenic effects of SMBJD in vitro and in tumour-bearing acute myeloid leukaemia (AML) mouse models. MATERIALS AND METHODS: In vivo, the chicken chorioallantoic membrane (CAM) and BALB/c null mouse xenograft models were treated with SMBJD (0, 2, 4, and 8 mg/mL) for 48 h and for 2 weeks, respectively. Anti-angiogenic activity was assessed according to microvessel density (MVD) and immunohistochemistry (IHC) targeting CD31 and VEGFR2. In vitro, proliferation viability, migratory activity and tube formation were measured. Western blots and polymerase chain reaction (PCR) assays were used to examine the levels of PI3K, Akt, and VEGF. RESULTS: HPLC analyses revealed the active constituents of SMBJD such as liquiritin, cimifugin, ferulic, isoferulic, and glycyrrhizic acids. In vitro, SMBJD treatment decreased cellular migration, chemotaxis, and tube formation at non-cytotoxic concentrations (2, 4, and 8 mg/mL) in a time- and dose-dependent manner. The dosage of less than IC(20) is considered safe. In vivo, CAM models exhibited a decrease in MVD, and the tissues of xenografted mice possessed reduced CD31 and VEGFR2 expression. Conditioned media (CM) from AML cells (HL60 and NB4 cells) treated with non-cytotoxic doses of SMBJD inhibited chemotactic migration and tube formation in vitro. Both CM (HL60) and CM (NB4) exhibited downregulated expression of PI3K, Akt, and VEGF. DISCUSSION AND CONCLUSIONS: SMBJD inhibited angiogenesis in AML through the PI3K/AKT pathway, which might be combined with targeted therapy to provide more effective treatment.