青蒿素衍生物抗癌活性研究

Anticancer Activity of Artemisinin Derivative

用MTT法检测了新青蒿素衍生物D-21对7种肿瘤细胞株及正常肝上皮细胞的抗增殖效果,并通过观察癌细胞形态、Hoechst 33258染色、Annexin V-FITC and PI染色和线粒体膜电位染色一系列实验,探讨新青蒿素衍生物D-21诱导人急性淋巴细胞白血病细胞凋亡的初步机制。结果表明:新青蒿素衍生物D-21对所选的肿瘤细胞系均有较好抗增殖作用,特别是对白血病细胞株K562,HL-60和CCRF-CEM具有显著细胞活性(IC 50分别为2.067±0.494,1.023±0.249,0.602±0.252μmol/L),且对L02的细胞毒性(IC 50=5.708±0.713μmol/L)低于阿霉素(IC 50=0.900μmol/L);经进一步研究,CCRF-CEM细胞经新青蒿素衍生物D-21处理后,可以通过线粒体膜电位凋亡途径来诱导癌细胞凋亡,并呈浓度和时间依赖性。说明新青蒿素衍生物D-21对癌细胞有极强的杀伤性,且细胞毒性低于现有药物阿霉素,有望成为新型抗癌药物的候选药物。

MTT method was used to detect the anti-proliferation effects of new artemisinin derivative D-21 on 7 tumor cell lines and normal liver epithelial cells,the preliminary mechanism of apoptosis induced by new artemisinin derivative D-21 in human acute lymphoblastic leukemia cells was investigated by observing the morphology of cancer cells,Hoechst 33258 staining,Annexin V-FITC and PI staining and mitochondrial membrane potential staining.The results show that the new artemisinin derivative D-21 has good anti-proliferation activity to the selected tumor cell lines,especially to leukemia cell lines K562,HL-60 and CCRF-CEM(IC 50=2.067±0.494,1.023±0.249,0.602±0.252μmol/L,respectively),and the cytotoxicity to L02(IC 50=5.708±0.713μmol/L)is lower than that of doxorubicin(IC 50=0.900μmol/L);CCRF-CEM cells can be induced apoptosis through mitochondrial membrane potential apoptosis pathway after treated with the new artemisinin derivative D-21 in a concentration-and time-dependent manner.It shows that the new artemisinin derivative D-21 is highly lethal to cancer cells,and its cytotoxicity is lower than that of the clinical drug doxorubicin,so it is expected to become a candidate for new anticancer drugs.