Zeng Dongfeng, Wang Jinliang, Kong Peiyan, Chang Cheng, Li Jieping, Li Jiali
Department of Hematology, Xinqiao Hospital, Third Military Medical University Chongqing, 400037, China.
Int J Clin Exp Pathol. 2014 Apr 15;7(5):2172-8. eCollection 2014.
Aberrant angiogenesis is essential to the development and progression of leukemia. Ginsenoside Rg3 has been commonly used in anti-angiogenic therapy of solid tumors. This study aimed to investigate the anti-angiogenic effects of Rg3 in patients with acute leukemia. Bone marrow stromal cells derived from patients with acute leukemia were treated with Rg3 and the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α) was detected by RT-PCR and western blot analysis. The results showed that Rg3 inhibited VEGF and HIF-1α expression at both mRNA and protein levels in bone marrow stromal cells. In addition, Rg3 treatment led to reduced serum levels of HIF-1α and VEGF in patients with acute leukemia. Mechanistically, we demonstrated that Rg3 downregulated the phosphorylation of Akt and ERK1/2 in BMSCs. In conclusion, Rg3 exhibits anti-leukemia effect in part due to its anti-angiogenic activity via inhibiting PI3K/Akt and ERK1/2 pathways, which act to regulate the expression of HIF-1α and VEGF.
异常血管生成对于白血病的发生和发展至关重要。人参皂苷Rg3已普遍用于实体瘤的抗血管生成治疗。本研究旨在探讨Rg3对急性白血病患者的抗血管生成作用。用Rg3处理急性白血病患者来源的骨髓基质细胞，通过RT-PCR和蛋白质印迹分析检测血管内皮生长因子（VEGF）和缺氧诱导因子1α（HIF-1α）的表达。结果显示，Rg3在mRNA和蛋白质水平均抑制骨髓基质细胞中VEGF和HIF-1α的表达。此外，Rg3治疗导致急性白血病患者血清中HIF-1α和VEGF水平降低。机制上，我们证明Rg3下调骨髓间充质干细胞中Akt和ERK1/2的磷酸化。总之，Rg3表现出抗白血病作用，部分原因是其通过抑制PI3K/Akt和ERK1/2途径的抗血管生成活性，这两条途径可调节HIF-1α和VEGF的表达。
