色霉素A_2诱导人肝癌HepG2细胞凋亡  

Chromomycin A_2 induces apoptosis of HepG2 cells in vitro

作　　者：王琰[1] 陆园园[2] 鲍维维[2] 谢美娟[2] 杜振宁[1] 

机构地区：[1]烟台大学药学院,山东烟台264005 [2]中国药科大学生物技术中心,江苏南京210009

出　　处：《南方医科大学学报》2014年第10期1449-1453,共5页Journal of Southern Medical University

基　　金：国家自然科学基金青年项目(81001395)~~

摘　　要：目的研究色霉素A2对人肝癌细胞HepG2的凋亡诱导作用,以期为肝癌的治疗提供新的治疗药物。方法 MTT法检测色霉素A2作用HepG2、MCF-7、A549、7901细胞后对细胞增殖的影响;激光共聚焦显微镜观察HepG2细胞在色霉素A2(0、60 nmol/L)的作用下,细胞染色质的变化;色霉素A2(0、20、40、60 nmol/L)作用HepG2细胞24 h,显微镜观察细胞形态变化,采用流式细胞术检测细胞凋亡率,活性氧水平及膜电位水平的变化。结果色霉素A2对人肝癌HepG2细胞具有明显的抑制效果,且呈时间,剂量依赖关系;药物作用细胞后,细胞染色质凝聚,染色加深;细胞形态方面发生细胞皱缩,并且细胞数目变少;流式细胞仪测定结果显示,细胞凋亡率随药物浓度升高而增大,并且细胞内活性氧水平上升,线粒体膜电位水平降低。结论色霉素A2诱导人肝癌HepG2细胞产生凋亡,其诱导HepG2细胞凋亡的机制可能与活性氧的升高及线粒体膜损伤有关。Objective To study the effect of chromomycin A2 in inducing apoptosis of HepG2 cells and explore the molecular mechanism. Methods HepG2, MCF- 7, A549, and 7901 cells were exposed to chromomycin A2 and the changes in the cell viability were detected using MTT assay. The changes in the chromatins were observed with laser scanning confocal microscope after incubation of the cells with chromomycin A2（60 nmol/L） for 24 h. The changes in cell morphology were examined with a phase- contrast microscope, and the apoptotic cell populations, fluorescent intensity of reactive oxygen species（ROS） and mitochondrial membrane potential were determined using flow cytometry. Results Chromomycin A2 significantly inhibited the proliferation of the cells in a time- and dose- dependent manner, and caused changes in the cell morphology and cell apoptosis. Exposure of the cells to chromomycin A2 resulted in chromatin condensation, ROS generation,and reduction of the mitochondrial membrane potential. Conclusion Increased ROS and mitochondria damage may importantly contribute to chromomycin A2-induced apoptosis in HepG2 cells.

关 键 词：肝癌 色霉素A2 细胞凋亡 活性氧 膜电位 线粒体 

分 类 号：R735.7[医药卫生—肿瘤]