呫吨酮并吡啶衍生物XP-16诱导人肺癌A549细胞凋亡  

XP-16,a new xanthono-pyridine derivative,induces apoptosis in human lung carcinoma A549 cells

作　　者：戴支凯[1] 杨成芳[1] 陈毅飞[1] 蒋君男 车冠华 覃江克[2] 

机构地区：[1]桂林医学院药理学教研室,广西桂林541004 [2]广西师范大学化学化工学院药用资源化学与药物分子工程国家重点实验室,广西桂林541004

出　　处：《中国药理学通报》2014年第6期838-842,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 21002015);广西自然科学基金资助项目(No 2010GXNSFB013013;0639030)

摘　　要：目的探讨呫吨酮并吡啶衍生物5,9-二(2-吡咯烷基乙酰氨基)-7H-吡啶并[4,3-c]呫吨-7-酮(XP-16)对人肺癌A549细胞的抗肿瘤作用及其可能作用机制。方法通过MTT法、细胞形态学和克隆实验观察XP-16对A549细胞增殖的影响;应用Hoechst 33258和PI双染法观察细胞凋亡;荧光分光光度计检测细胞内钙([Ca2+]i)及线粒体膜电位;qRT-PCR检测Bad和金属硫蛋白1A(metallothionein 1A,MT-1A)mRNA表达。结果 XP-16能抑制A549细胞增殖,呈剂量和时间依赖性。XP-16作用A549细胞24 h后,A549细胞出现染色质聚集、核碎裂等典型的凋亡形态学改变;随XP-16剂量的增加,A549细胞凋亡百分率逐渐增大。XP-16作用后,A549细胞的[Ca2+]i和线粒体膜电位降低、Bad和MT-1A mRNA的表达增加。结论 XP-16具有诱导A549细胞凋亡的作用,可能与其降低[Ca2+]i和线粒体膜电位有关。MT-1A表达的上调可能是[Ca2+]i降低的结果。Aim To investigate the anticancer effect of a new xanthono-pyridine derivative N, N ＇-（ 7-oxo-7H-chromeno[3,2-h] quinoline-5,9-diyl）-bis（2-（ pyrroli-din-1-yl）acetamide） （XP-16） on human lung carcino-ma cell line A549 and the potential mechanism. Meth-ods Antiproliferative effect of XP-16 on A549 cells was evaluated by MTT assay, morphological examina-tion and colonial assay. Apoptosis detection was car-ried out using Hoechst 33258 and PI double-dyeing method. Intracellular Ca2＋ concentration （ [ Ca2＋] i ） and mitochondria membrane potential were detected by fluorospectrophotometer. A549 cells treated with XP-16 were collected for Bad and metallothionein 1 A （ MT-1 A ） transcript analysis by real-time reverse tran-scriptase-polymerase chain reaction （ qRT-PCR） . Re-sults XP-16 inhibited A549 cell proliferation in dose-and time-dependent manner. Typical apoptotic morphology such as chromatin aggregation and nuclear fragmentation was observed in A549 cells treated with XP-16 for 24 h, and the apoptosis was showed in a dose-dependent manner. After treated with XP-16, [ Ca2＋] i and mitochondria membrane potential of A549 cells were decreased, and relative mRNA level of Bad and MT-1A was up-regulated. Conclusions XP-16 has anticancer effect on A549 cells through apoptosis, which might be associated with decreasing intracellular Ca2＋ concentration and mitochondria membrane poten-tial. Up-regulation of MT-1A expression might be the result of decreased [ Ca2＋] i .

关 键 词：5 9-二(2-吡咯烷基乙酰氨基)-7H-吡啶并[4 3-c] 呫吨-7-酮 人肺癌A549细胞 线粒体膜电位 凋亡 金属硫蛋白1A 细胞内钙 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R329.25[医药卫生—基础医学]