呫吨酮并吡啶衍生物XP-16抗人胃癌MGC-803细胞作用  

Anticancer Effect of Xanthono-Pyridine Derivative XP-16 on Human Gastric Carcinoma MGC-803 Cells

作　　者：黄姣娥[1] 蒋君男 车冠华 覃江克[2] 戴支凯[1] 

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：《中国药学杂志》2014年第15期1315-1320,共6页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(21002015);广西自然科学基金资助项目(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)抗人胃癌MGC-803细胞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MGC-803细胞增殖;应用Hoechest33258和PI双染法观察细胞凋亡;采用荧光分光光度计检测细胞内钙([Ca2+]i)及线粒体膜电位;RT-PCR检测Bad和金属硫蛋白1A(MT-1A)mRNA的表达。结果 XP-16能抑制MGC-803细胞增殖,呈浓度(r=0.88,P<0.01)和时间(r=0.93,P<0.05)依赖性。XP-16作用MGC-803细胞24 h后,MGC-803细胞出现染色质聚集、核碎裂等典型的凋亡形态学改变,且随XP-16浓度的增加,MGC-803细胞凋亡百分率逐渐增大。XP-16作用后,MGC-803细胞的[Ca2+]i和线粒体膜电位降低、Bad和MT-1A mRNA表达增加。结论 XP-16可通过诱导细胞凋亡抑制MGC-803细胞增殖,其机制可能与其降低[Ca2+]i和线粒体膜电位有关,而细胞内MT-1A表达的上调可能是[Ca2+]i下降的结果。OBJECTIVE To investigate aticancer effect and potential mechanism of a new xanthono-pyridine derivative N,N＇-（7- oxo-7H-chromeno[3,2-h] quinoline-5,9-diyl）-bis （2-（pyrrolidin-1-yl） acetamide） （XP-16） on human gastric carcinoma cell line MGC-803. METHODS Antiproliferative effect of XP-16 on MGC-803 cells was evaluated by MTF assay, morphological examination and colonial assay. Apoptosis detection was carried out using Hoeehest33258 and PI double-dyeing method. Intracellular calcium con- centration （ [Ca2 ＋ ] i ） and mitoehondria membrane potential were detected by fluorospectrophotometer. Bad and metallothionein 1A （MT-1A） transcripts were analyzed by real-time reverse transcriptase-polymerase chain reaction （RT-PCR）. RESULTS XP-16 could inhibit proliferation of MGC-803 cells in dose- and time-dependent manner（ r = 0. 88, P 〈 0. 01 ; r = 0. 93, P 〈 0. 05 ）. Typical apoptotic morphology such as chromatin aggregation and nuclear fragmentation was observed in MGC-803 ceils with XP-16-treated for 24 h, and the effect was dose-dependent. After treated with XP-16, [ Ca2 ＋ ] i and mitochondria membrane potential of MGC-803 cells were decreased, relative mRNA levels of Bad and MT-1A were up-regulated. CONCLUSION XP-16 can inhibite MGC-803 cells proliferation by inducing apoptosis, which might be associated with decreasing [ Ca2＋ ] i and mitochondria membrane potential. 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 人胃癌MGC-803细胞 凋亡 细胞内钙 线粒体膜电位 金属硫蛋白1A 

分 类 号：R965[医药卫生—药理学]