青蒿琥酯对K562细胞的抑制作用及对VEGF表达的影响

本研究探讨青蒿琥酯（artesunate，ART）对K562的抑制作用和对VEGF表达的影响，为青蒿琥酯可能成为一种新的抗白血病药物提供实验基础和理论依据。实验以K562细胞为靶细胞．设对照组及各ART浓度（12．5、25、50、100μg／ml）组，绘制其生长曲线。用光学显微镜观察K562细胞生长情况及不同浓度ART作用不同时间后的细胞形态变化，同时用ELISA检测ART作用K562前后细胞上清液中VEGF含量变化.结果表明：ART对K562细胞的生长有明显的抑制作用（P〈0．01），ART在抑制K562细胞生长时也下调其VEGF的表达（P〈0．01）。K562细胞抑制率与其上清液中的VEGF浓度的相关分析表明：随着各ART组作用浓度递增，在一定时间范围内K562细胞抑制率升高，与此同时K562细胞VEGF表达下调，此变化差异有显著统计学意义（P〈0.01）。结论：青蒿琥酯能显著地抑制K562细胞的生长；青蒿琥酯在抑制K562细胞生长时对VEGF的表达明显下调，K562细胞抑制率与其VEGF表达呈负相关；青蒿琥酯抑制K562细胞生长的机制可能是通过下调细胞的VEGF的表达实现的。

Suppressive Effect of Artesunate on K562 Cell Growth and Its Influence on VEGF Expression

The aim of this study was to investigate the inhibitive effect of artesunate (ART) on CML cell line K562 and its influence on VEGF expression in vitro. Human CML cell line K562 cells were cultured in RPMI 1640 medium supplemented with 10% heat-inactivated fetal calf serum. All cells were cultured in a humidified atmosphere of 5% CO2 at 37.0 degrees C. K562 cells in logarithmic growth phase were collected and seeded in RPMI-1640 medium, and were treated with ART. At the indicated time points, viable cells were counted by trypan blue exclusion method. Each assay was triplicated. K562 cells were treated with ART at different concentrations. Morphological changes were observed with invert microscope. VEGF expression in K562 cells treated with ART at different concentrations and in the control group were detected by enzyme-linked immunosorbent assay (ELISA). The results indicated that ART obviously induced growth inhibition in K562 cells. The relationship between cell inhibition rates and the concentrations of ART showed a dose-dependent manner (p < 0.01). VEGF expression of K562 cells treated with ART at different concentrations decreased significantly (p < 0.01). No significant change of VEGF expression in control group was observed (p > 0.05), while VEGF expression was down-regulated significantly in experiment groups (p < 0.01). The inhibition rate of K562 cells increased in time and concentration-dependent manners. In K562 cell lines treated with ART, VEGF expression was up-regulated at first and then down-regulated to a lower level. It is concluded that ART inhibits k562 cell proliferation in a dose and time dependent manner. The mechamism underlying the inhibitive effect of ART on K562 cells may be realized through down-regulation of VEGF expression.