Department of Hematology, No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Hematology, Jiangsu Province Hospital of TCM, The Affiliated Hospital of Nanjing University of TCM, Nanjing, China.
Pharm Biol. 2020 Dec;58(1):454-464. doi: 10.1080/13880209.2020.1764059.
ShengMaBieJia decoction (SMBJD) is used to treat solid and hematological tumours; however, its anti-angiogenesis activity remains unclear. This study verified the anti-angiogenic effects of SMBJD and in tumour-bearing acute myeloid leukaemia (AML) mouse models. , 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. , 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. HPLC analyses revealed the active constituents of SMBJD such as liquiritin, cimifugin, ferulic, isoferulic, and glycyrrhizic acids. , 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 is considered safe. , 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 . Both CM (HL60) and CM (NB4) exhibited downregulated expression of PI3K, Akt, and VEGF. SMBJD inhibited angiogenesis in AML through the PI3K/AKT pathway, which might be combined with targeted therapy to provide more effective treatment.
升麻鳖甲汤（SMBJD）用于治疗实体瘤和血液系统肿瘤，但它的抗血管生成活性尚不清楚。本研究验证了 SMBJD 在荷瘤急性髓系白血病（AML）小鼠模型中的抗血管生成作用。采用鸡胚尿囊膜（CAM）和 BALB/c 裸鼠异种移植模型，分别用 SMBJD（0、2、4 和 8mg/ml）处理 48 小时和 2 周。根据微血管密度（MVD）和针对 CD31 和 VEGFR2 的免疫组织化学（IHC）评估抗血管生成活性。还测量了增殖活力、迁移活性和管形成。Western blot 和聚合酶链反应（PCR）检测用于检查 PI3K、Akt 和 VEGF 的水平。HPLC 分析揭示了 SMBJD 的活性成分，如甘草苷、毛蕊异黄酮、阿魏酸、异阿魏酸和甘草酸。结果表明，SMBJD 处理在非细胞毒性浓度（2、4 和 8mg/ml）下以时间和剂量依赖性方式降低了细胞迁移、趋化性和管形成。低于 IC 的剂量被认为是安全的。CAM 模型显示 MVD 降低，异种移植小鼠组织中 CD31 和 VEGFR2 表达减少。用 SMBJD 的非细胞毒性剂量处理的 AML 细胞（HL60 和 NB4 细胞）的条件培养基（CM）抑制趋化性迁移和管形成。CM（HL60）和 CM（NB4）均表现出 PI3K、Akt 和 VEGF 的表达下调。SMBJD 通过 PI3K/AKT 通路抑制 AML 的血管生成，这可能与靶向治疗相结合，提供更有效的治疗。
