糖原合酶激酶-3β磷酸化抑制顺铂诱导卵巢癌细胞凋亡的研究  

Enhanced p-GSK-3β Inhibits the Apoptosis Induced by Cisplatin in Ovarian Carcinoma Cells

作　　者：宋晓红[1,2] 翁丹卉[1] 邢辉[3] 卢运萍[1] 王世宣[1] 马丁[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院妇产科,武汉430030 [2]首都医科大学附属北京佑安医院妇产科,北京100069 [3]华中科技大学同济医学院附属襄樊中心医院妇产科,襄樊441021

出　　处：《华中科技大学学报（医学版）》2009年第5期645-648,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金(No.30571950);海外青年学者合作研究基金(No.30528012);国家重点基础研究发展规划基金(No.2002CB51-3107)资助项目

摘　　要：目的探讨增加糖原合酶激酶-3β(GSK-3β)的磷酸化状态对顺铂诱导的卵巢癌细胞凋亡的作用。方法体外培养人卵巢癌细胞株OV2008细胞,运用GSK-3β特异性抑制剂LiCl增加磷酸化GSK-3β的表达,应用流式细胞仪检测不同浓度顺铂诱导的细胞凋亡,Western blot检测GSK-3β及磷酸化GSK-3β蛋白的表达。结果流式细胞仪检测结果显示,梯度增加的顺铂(40、80、120μmol/L)作用于OV2008细胞24 h,其凋亡率不断增加,分别为(4.55±1.64)%、(25.50±0.94)%和(53.80±1.62)%;而应用抑制剂预孵育的细胞,不同浓度顺铂作用24 h后凋亡率分别为(2.10±0.80)%(、15.75±0.97)%和(20.45±0.87)%;Western blot显示,抑制剂LiCl作用后,细胞的磷酸化GSK-3β表达明显增加,并且顺铂作用亦可引起磷酸化GSK-3β表达上调;流式结果还显示,PI3K的特异性抑制剂LY294002作用后使顺铂诱导的细胞凋亡率从(18.75±0.70)%增加至(28.40±1.50)%。结论磷酸化GSK-3β表达增加可抑制顺铂诱导的卵巢癌细胞的凋亡。Objective To investigate the effects of enhanced glycogen synthase kinase-3β phosphorylation（p-GSK3-β）on the apoptosis induced by cisplatin in ovarian carcinoma cells.Methods Human ovarian carcinoma cell line OV2008 cells were cultured in vitro.LiCl was used to enhance the expression of p-GSK3-β.The apoptosis was detected in OV2008 cells induced by different concentrations of cisplatin by FACS.The expression of GSK3-β and p-GSK3-β was measured by Western blot.Results The results of FACS showed that the apoptotic rate of OV2008 cells treated with different concentrations of cisplatin（40,80,and 120 μmol/L）was（4.55±1.64）%,（25.50±0.94）% and（53.80±1.62）%.After pretreatment with LiCl,the apoptotic rate of OV2008 cells treated with different concentrations of cisplatin for 24 h was reduced to（2.1±0.80）%,（15.75±0.97）% and（20.45±0.87）% respectively.Western blot revealed that LiCl could enhance the expression of p-GSK3-β and the cisplatin also could up-regulate the expression of p-GSK3-β.FACS also demonstrated that LY294002,the PI3K specific inhibitor,could increase the apoptotic rate of OV2008 cells induced with cisplatin from（18.75±0.70）% to（28.40±1.50）%.Conclusion The augment of p-GSK3-β expression could inhibit the cisplatin-induced apoptosis in ovarian carcinoma cells.

关 键 词：糖原合酶激酶-3Β 顺铂 细胞凋亡 卵巢癌 

分 类 号：R737.33[医药卫生—肿瘤]