青蒿琥酯对人淋巴细胞白血病/淋巴瘤细胞抑制作用及机理的研究

目的 观察青蒿琥酯(ART)对白血病/淋巴瘤细胞株Raji、Jurkat和急性淋巴细胞白血病(ALL)原代细胞的增殖抑制作用,以及ART与长春新碱(VCR)、阿糖胞苷(Ara-C)的细胞毒协同效应,并探讨其作用机制.方法 MTT法观察ART对Raji、Jurkat、ALL原代细胞的增殖抑制效应及ART与VCR、Ara-C的协同效应.Wright-Giemsa染色光镜下及透射电镜观察细胞凋亡的形态变化,Rhodamine-123检测线粒体跨膜电位(MMP)变化,比色法检测细胞内caspase-3浓度变化.结果 ART在体外能显著抑制Raji、Jurket细胞的增殖,对ALL原代细胞亦具有增殖抑制作用.低浓度ART与VCR、Ara-C联合,能增加VCR、Ara-C的细胞毒作用.ART作用后B/T淋巴细胞白血病/淋巴瘤细胞光镜及电镜均表现出凋亡形态学改变,线粒体跨膜电位下降,细胞内caspase-3的表达增加,呈浓度依赖性.与对照组相比,差异具有统计学意义(P<0.05).结论 ART对淋巴细胞白血病/淋巴瘤细胞具有抑制作用,且与VCR、Ara-C联用具有协同效应,其机制与诱导肿瘤细胞凋亡有关.ART有望开发成治疗ALL/淋巴瘤的新药.

Inhibitive Effect of Artesunate on Human Lymphoblastic Leukemia/Lymphoma Cells

Objective To test the effect of Artesunate (ART) on the proliferation of Raji cells, Jurkat cells and acute lymphoblastic leukemia (ALL) primary cellst to determine the synergistic antiproliferation effect between ART and Vincristine (VCR) or Cytarabine(Ara-C) on Raji and Jurkat cells; and to explore the mechanism of ART induced apoptosis of tumor cells in vitro. Methods MTT assay was performed to detect the inhibition of proliferation of Raji, Jurkat, and ALL primary cells. The cells were exposed to ART at various concentrations with or without VCR or Ara-C. The morphological changes of Raji and Jurkat cells were observed under light microscopy after Wright-Giemsa dyeing and electron transmission microscopy. The mitochondria transmenbrane potential was measured by Rhodamine 123 staining. Colorimetric method was used to measure the activities of caspase-3 in those tumor cells. Results ART inhibited the proliferation of Raji cells, Jurkat cells and ALL primary cells. The cytotoxicity of ART on Raji cells and Jurkat cells at a low concentration increased when combined with VCR or Ara-C. Apoptosis in Raji cells and Jurkat cells appeared after exposure to ART. Raji cells and Jurkat cells exposed to ART showed mitochondria transmembrane potential collapse. ART increased the caspase-3 activities of Raji, Jurkat and ALL primary cells. Conclusion ART alone or combined with chemotherapy drugs could inhibit the proliferation of B/T lymphocytic tumor cell lines as well ALL primary cells in vitro, probably through the mechanism of apoptosis, which suggest that ART is likely to be a potential drug in the treatment of leukemia / lymphoma.