姜黄素类似物B67诱导细胞凋亡和G_2/M期阻滞增强对鼻咽癌辐射抗拒细胞的抑制作用  

Curcumin analogue B67 induces apoptosis and G_2/M arrest to suppress radioresistant nasopharyngeal carcinoma cells

作　　者：原玉芬[1] 王杜娟[1] 潘运宝[1] 梁广[2] 肖健[2] 王苏美[1] 杨惠玲[1] 

机构地区：[1]中山大学中山医学院病理生理学教研室,广东广州510080 [2]温州医学院药学院,浙江温州325085

出　　处：《中国病理生理杂志》2011年第3期504-508,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30670627);广州市科技计划资助项目(No.2009Z1E2012);广东省科技计划资助项目(No.2008A03020/009)

摘　　要：目的:研究姜黄素类似物B67对鼻咽癌(NPC)辐射抗拒细胞(CNE-2R)活性和增殖的作用,及其对细胞周期和凋亡的影响。方法:采用MTT和平板克隆形成实验检测B67对CNE-2R细胞及其母细胞CNE-2活性和增殖的抑制作用,采用荧光显微镜和流式细胞仪观测凋亡细胞的形态学变化、细胞凋亡百分率、细胞周期分布和线粒体膜电位的改变,采用裸鼠皮下成瘤实验检验B67作用于CNE-2R细胞后的成瘤性。结果:B67作用于NPC细胞24、48和72 h后,MTT检测细胞活性的IC50分别为3.96、2.59和0.89μmol/L(CNE-2R)以及8.84、3.55和1.10μmol/L(CNE-2),B67作用48 h后平板克隆形成实验检测NPC细胞增殖的IC50分别为0.55μmol/L(CNE-2R)和0.73μmol/L(CNE-2),B67作用24 h后NPC细胞的G2/M期比例的上升分别为5.32%上升到40.01%(CNE-2R)和9.07%上升到15.73%(CNE-2),B67作用48 h后NPC细胞凋亡率的改变分别为5.49%上升到38.06%(CNE-2R)和4.99%上升到35.74%(CNE-2),B67作用48 h后NPC细胞线粒体膜电位的下降分别为66.76%(CNE-2R)和72.09%(NE-2),B67作用24 h后NPC细胞在裸鼠皮下的成瘤率分别为0%(CNE-2R)以及低浓度组100%、高浓度组0%(CNE-2)。结论:姜黄素类似物B67可较特异地诱导CNE-2R细胞G2/M期阻滞和促进细胞凋亡和线粒体膜电位的改变,引起裸鼠皮下成瘤性的差异,以增强其对鼻咽癌辐射抗拒细胞的抑制作用。AIM： To study the effect of curcumin analogues B67 on radioresistant nasopharyngeal carcinoma cells（CNE-2R）. METHODS： The effects of B67 on the cell viability and proliferation of CNE-2R and the parent cells CNE-2 were detected by MTT assay and colony formation assay,respectively.The changes of cell cycle,apoptosis and mitochondrial membrane potential were determined by flow cytometry.The morphological changes of the cells were observed under fluorescence microscope.Node mice were subcutaneously inoculated with the cells to determine the tumorigenic ability. RESULTS： The IC50 of B67 on the viability of CNE-2R cells after treatment for 24 h,48 h and 72 h were 3.96,2.59 and 0.89 μmol/L,respectively,and those of CNE-2 cells were 8.84,3.55 and 1.10 μmol/L,respectively.The IC50 of B67 on the proliferation of CNE-2R cells after treatment for 48 h was 0.55 μmol/L,and that of CNE-2 cells was 0.73 μmol/L.After treated with B67 for 24 h,CNE-2R and CNE-2 cells at G2/M stage increased from 5.32% to 40.01% and from 9.07% to 15.73%,respectively.After treated with B67 for 48 h,the apoptosis of CNE-2R and CNE-2 cells increased from 5.49% to 38.06% and from 4.99% to 35.74%,respectively.The mitochondrial membrane potential in CNE-2R and CNE-2 cells was decreased by 66.76% and 72.09%,respectively.After treated with B67 for 24 h,the tumorigenic rate of CNE-2R cells was 0%,while the rates of CNE-2 cells in low-and high-concentration groups were 100% and 0%,respectively. CONCLUSION： Curcumin analogue B67 exhibits enhanced suppressive activity on radioresistant nasopharyngeal carcinoma cells by inducing G2/M-phase arrest,promoting cell apoptosis and changing mitochondrial membrane potential.

关 键 词：姜黄素 鼻咽肿瘤 辐射耐受 细胞周期 细胞凋亡 

分 类 号：R363[医药卫生—病理学]