Lee Jun, Zhou Hui-Jun, Wu Xiu-Hua
Department of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310031, PR China.
Cancer Chemother Pharmacol. 2006 Jan;57(2):213-20. doi: 10.1007/s00280-005-0002-y. Epub 2005 Aug 2.
Dihydroartemisinin (DHA), a more water-soluble active metabolite of artemisinin derivatives, is safe and the most effective antimalarial analog of artemisinin. In the present investigation, we assessed the effect of DHA on vascular endothelial growth factor (VEGF) expression and apoptosis in chronic myeloid leukemia (CML) K562 cells. The results demonstrated that in addition to its antiproliferation effect on CML cells, DHA was also found to induce K562 cells apoptosis. The percentage of apoptotic cells was increased to 6.9 and 15.8% after being treated with 5 and 10 micromol/l DHA for 48 h, respectively (P<0.001). In order to analyze the effect of DHA on VEGF expression in K562 cells, we assessed the level of VEGF expression by western blot; detected the form of VEGF mRNA by RT-PCR and examined the level of VEGF secreted in conditioned media (CM) by ELISA assay. All these experiments suggested that DHA could inhibit the VEGF expression and secretion effectively in K562 cells, even at a lower concentration (2 micromol/l, P<0.05). Moreover, we further assessed the stimulating angiogenic activity of CM from K562 cells on CAM model. The angiogenic activity was decreased in response to the CM from K562 cells pretreated with DHA in a dose-dependent manner. Taken together, these results from our study together with its known low toxicity make it possible that DHA might present potential antileukemia effect as a treatment for CML therapy, or as an adjunct to standard chemotherapeutic regimens.
双氢青蒿素（DHA）是青蒿素衍生物中水溶性更强的活性代谢产物，安全且是青蒿素最有效的抗疟类似物。在本研究中，我们评估了双氢青蒿素对慢性髓性白血病（CML）K562细胞中血管内皮生长因子（VEGF）表达及细胞凋亡的影响。结果表明，双氢青蒿素除了对CML细胞有抗增殖作用外，还能诱导K562细胞凋亡。用5和10微摩尔/升双氢青蒿素处理48小时后，凋亡细胞百分比分别增至6.9%和15.8%（P<0.001）。为分析双氢青蒿素对K562细胞中VEGF表达的影响，我们通过蛋白质印迹法评估VEGF表达水平；通过逆转录聚合酶链反应检测VEGF mRNA的形式，并通过酶联免疫吸附测定法检测条件培养基（CM）中分泌的VEGF水平。所有这些实验表明，双氢青蒿素即使在较低浓度（2微摩尔/升，P<0.05）下也能有效抑制K562细胞中VEGF的表达和分泌。此外，我们进一步评估了K562细胞条件培养基在鸡胚绒毛尿囊膜（CAM）模型上的促血管生成活性。用双氢青蒿素预处理的K562细胞条件培养基诱导的血管生成活性呈剂量依赖性降低。综上所述，我们研究的这些结果及其已知的低毒性表明，双氢青蒿素可能作为CML治疗的潜在抗白血病药物，或作为标准化疗方案的辅助药物。
