诺帝对CXCR4介导的人恶性胶质瘤细胞钙流和白细胞介素8分泌的抑制作用

目的 观测诺帝(Nordy)对人恶性胶质瘤细胞系U87细胞趋化因子受体CXCR4活化后钙流变化及白细胞介素8(IL-8)产生的影响.方法 采用Fluo-4/AM标记钙离子、激光共聚焦显微术观测CXCR4被其配体间质细胞衍生因子-1α(SDF-1α)活化后U87细胞钙流的变化,并通过酶联免疫吸附试验(ELISA)检测细胞培养上清中IL-8的含量;以CXCR4抑制剂AMD3100为对照,用自行合成的化合物诺帝顸处理U87细胞,再用SDF-1α刺激,观测二者对CXCR4活化后引起的钙流变化和IL-8分泌的影响.结果 25～100ng/ml SDF-1α可不同程度地引起U87细胞胞内钙流增加和IL-8分泌量增多,与对照组(无SDF-1α刺激)相比均有显著统计学意义(P<0.05);用1～10μmol/LAMD3100或25～100μmol/L诺帝预处理细胞,再用SDF-1α刺激,上述效应受到抑制.结论 诺帝可抑制CXCR4活化引起的钙流和IL-8产生,这可能是其抗胶质瘤血管生成机制之一.

Nordy inhibits functional CXCR4-induced calcium mobilization and production of IL-8 in malignant human glioma cells

Objective To investigate the effect of anti-cancer agent Nordy on functional CXCR4-induced calcium mobilization and production of interleukin-8 (IL-8) in human malignant glioma cells. Methods Fluo-4/AM was used as a fluorescent calcium indicator. Calcium mobilization induced by stromal cell-derived factor-1α (SDF-1α) was measured by confocal laser scanning microscopy. Production of IL-8 was measured by enzyme-linked immunosorbent assay (ELISA). To observe the effect of AMD3100, a CXCR4 inhibitor, and Nordy on CXCR4-induced calcium mobilization and production of IL-8, cells were pretreated by AMD3100 or Nordy before SDF-1α stimulation. Results Compared with control group, the stimulation of 25～100ng/ml SDF-1α elicited elevation of calcium and increased IL-8 secretion, which could be inhibited by pretreatment with 1～10μmol/L AMD3100 or 25～100μmol/L Nordy. Conclusions Nordy inhibits CXCR4-induced calcium mobilization and IL-8 secretion, which might be the possible antiangiogenesis mechanism of Nordy.