癌变·畸变·突变 ›› 2008, Vol. 20 ›› Issue (5): 350-353.doi: 10.3969/j.issn.1004-616x.2008.05.004

• 论著 • 上一篇    下一篇

野鸦椿对HeLa细胞的抗增殖作用及其机制的初步研究

左 敏1/ 倪志宇1/ 许 立1/ 于 峰1/ 吕 飒2/ 陈仕萍2/ 广田满3/ 铃木信夫2/ 董 玫1,   

  1. 1.河北医科大学法医学系,河北 石家庄 050017 ;2.千叶大学医学部环境影响生物化学教室,日本 千叶县千叶市;3.信州大学农学部生理活性化学教室,日本 长野县伊那市
  • 收稿日期:2007-11-28 修回日期:2008-01-08 出版日期:2008-09-30 发布日期:2008-09-30

Anti_proliferative Activity and the Mechanisms of Euscaphis Japonica Kanitz in HeLa

ZUO Min1, NI Zhi_yu1, XU Li1, YU Feng1, LU Sa2,CHEN Shi_ping2, Hitota Mituru3, Suzuki Nobuo2,DONG Mei1,   

  1. 1.Faculty of Forensic Medicine, the School of Basic Medical Sciences, Hebei Medical Univercity, Shijiazhuang 050017,China;2. Department of Environmental Biochemistry, Graduate School of Medicine,Chiba University, Inohana 1_8_1,Chuoku,Chiba 260_8670,Japan; 3.Department of Bioscience and Biotechnology, Faculty of Agriculture, Shinshu University, Nagano 399_4598,Japan
  • Received:2007-11-28 Revised:2008-01-08 Online:2008-09-30 Published:2008-09-30

摘要: 背景与目的: 从野鸦椿(euscaphis japonica kanitz)枝叶的甲醇提取物分离纯化得到3种酯类化合物7_hydroxy_2_octen_5_olide (1),methyl 5,7_dihydroxy_2 (Z)_octenoate (2)和3,7_dihydroxy_5_octanolide (3),对这3种酯类化合物的抗肿瘤细胞增殖作用及其机制进行研究。 材料与方法: 利用四唑盐(MTT)比色法测定这3种酯类化合物对HeLa细胞增殖的抑制作用;采用流式细胞术检测化合物1对HeLa细胞的凋亡和P53蛋白表达的影响;利用电镜观察化合物1引起 HeLa细胞的形态学改变。 结果: 化合物1和化合物2对体外培养的HeLa细胞的增殖均具有明显地抑制作用,并有较好量效关系,对HeLa细胞增殖的半数抑制浓度分别为49.34 μmol/L和24.53 μmol/L;流式细胞学检查发现化合物1处理后的HeLa细胞发生凋亡,且P53蛋白表达增加,与对照组比较差异有统计学意义(P<0.01);电镜下可见化合物1引起 HeLa细胞凋亡的形态学改变。 结论: 野鸦椿的提取物7_hydroxy_2_octen_5_olide(1)和methyl 5,7_dihydroxy_2 (Z)_octenoate(2)能抑制体外培养的HeLa细胞的增殖,其作用机制可能与调节HeLa细胞P53蛋白表达及诱导HeLa细胞的凋亡有关。

关键词: 野鸦椿, 酯类化合物, 抗肿瘤细胞增殖活性, 细胞凋亡, P53

Abstract: BACKGROUND AND AIM: In order to investigate the anti_proliferative activity against HeLa cell line and to explore the possible mechanism of three natural compounds: 7_hydroxy_ 2_octen_5_olide (1), methyl 5,7_dihydroxy_2 (Z)_octenoate (2) and 3,7_dihydroxy_5_octanolide (3) isolated from leaves of Euscaphis japoneca Kantiz. MATERIALS AND METHODS: The anti_proliferative effects of the three compounds on HeLa cells were tested by MTT assay in vitro. The apoptosis induced by above three compounds was studied by FCM. The morphological changes of HeLa cells were examined by transmission electron microscope. RESULTS: Compounds 1 and 2 exhibited dose_dependent anti_proliferative activity on cultured HeLa cells. The concentrations of compounds 1 and 2 resulting in 50% survival rates (IC50) for HeLa cells were 49.34 μmol/L and 24.53 μmol/L, respectively. Comparing with the control group, the apoptosis rate and the expression of P53 in HeLa cells were markedly higher for compound 1 group (P<0.01). The morphological changes of HeLa cells incubated with compound 1 showed chromatin condensation, marginal and nuclear fragmentation. CONCLUSION: 7_Hydroxy_2_octen_5_olide and methyl 5, 7_dihydroxy_2 (Z)_octenoate isolated from the leaves of Euscaphis japoneca Kanitz could inhibit the proliferation of HeLa cells in vitro. Its anti_prolifrative activity might be associated with upregulating the expression of P53 and inducing the occurrence of apoptosis.

Key words: euscaphis japoneca kanitz, esters compounds, anti_proliferative activity, apoptosis, P53