红花桑寄生总黄酮提取物增强多柔比星抗白血病效果及其相关机制研究

Nispex,an Extract of Scurrula parasitica L.on Nernium indicum Mill.,Enhancing Anti-leukaemia of Adriamycin Maybe Relevant to Suppression of NF-κB and VEGF

以人急性髓系白血病细胞株HL-60裸鼠移植瘤为模型,研究了一种寄主为夹竹桃的红花桑寄生总黄酮提取物(Nispex)与多柔比星联用的抗白血病效果及其可能的作用机制。以抑瘤率为指标,采用药物相互作用指数(CDI)来评价药物联合作用疗效。10mg/kg/d Nispex腹腔给药(连续给药9d)与15mg/kg多柔比星(尾静脉一次性给药,下同)联用对HL-60移植瘤有较好的抑制作用,抑瘤率89%,CDI为0.43(P<0.01);与10mg/kg多柔比星联用,抑瘤率为57%,CDI值为0.80(P<0.05)。说明Nispex与多柔比星有较好的协同抗白血病作用。采用EMSA、Western blot和免疫荧光染色分析了Nispex对HL-60细胞中NF-κB的影响,结果表明Nispex可降低了NF-κB的DNA结合活性,下调NF-κBp65蛋白的表达,也抑制NF-κB的核转移,说明Nispex是一种天然NF-κB抑制剂。ELISA分析表明Nispex可下调HL-60细胞分泌VEGF。

Nispex is a flavonoids extract of Scurrula parasitica L. parasitized on Nernium indicum Mill.. In this study, xenograft was established by subcutaneous implantation of cultured HL-60 cells in BALB/c nu/nu mice to evaluation the anti-leukaemia activity of Adriamycin in combination with Nispex in vivo. Coefficient of drug interaction （CDI） was employed to evaluate the drugs synergistic effects. 10 mg/kg per day Nispex （treated 9 days,ip） in combination with 15 mg/kg ADR （injected through caudal veln,once only at the first day,the same below. ） inhibited 89% tumor growth, CDI was 0. 43 （ P 〈 0. 01 ） ; inhibited 57% tumor growth when combined with 10 mg/kg ADR, CDI was 0. 80 （ P 〈 0. 05）. Nispex enhanced the anti-leukaemla activity of ADR significantly. Nispex was confirmed to be a natural inhibitor of NF-κB pathway by EMSA,Western blot and immunofluorescence assay. VEGF levels were reduced significantly in the supematant of HL-60 cell cultures when treated by Nispex, detected by ELISA.