溶血磷脂酸抑制顺铂诱导卵巢癌细胞凋亡机制的研究  

Mechanisms involved in lysophosphatidic acid inhibited apoptosis induced by cisplatin in ovarian carcinoma cells

作　　者：丁萍萍 李强[1] 

机构地区：[1]山东大学附属省立医院妇产科,济南250021

出　　处：《现代妇产科进展》2011年第12期965-968,共4页Progress in Obstetrics and Gynecology

基　　金：山东省优秀中青年科学家科研奖励基金(No:03BS034)

摘　　要：目的:探讨溶血磷脂酸(LPA)抑制顺铂(DDP)诱导卵巢癌细胞凋亡的机制。方法:体外培养人卵巢上皮癌细胞株SKOV3,选用促分裂素原活化蛋白激酶(MAPK)信号传导通路特异性阻断剂PD98059,应用四甲基偶氮唑蓝(MTT)比色法测定DDP、DDP+LPA和DDP+LPA+PD98059对SKOV3细胞增殖活性的影响;应用Ho-echst33258荧光染色观察凋亡细胞;应用实时荧光定量PCR(RT-PCR)测定单用LPA或合用PD98059对SKOV3细胞环氧化酶-2(COX-2)表达的影响;应用流式细胞仪(FCM)测定细胞凋亡及细胞周期的变化。结果:LPA对DPP抑制卵巢癌细胞增殖有拮抗作用,且增加S期细胞比率;联合应用PD98059后,卵巢癌细胞生长受抑制,S期比率降低,而凋亡小体产生增多。RT-PCR结果显示,LPA能促进COX-2表达(P<0.05),而合用PD98059后COX-2表达降低(P<0.05)。结论:LPA通过MAPK信号传导通路抑制顺铂诱导的卵巢癌细胞凋亡,且与COX-2表达有关。Objective： To investigate the mechanisms of lysophosphatidic acid inhibited apoptosis induced by cisplatin in ovarian carcinoma cells.Methods： Human ovarian cancer cell line（SKOV3）was cultured,and MAPK inhibitor（PD98059）was used.The proliferation of SKOV3 cells stimulated by DDP,DDP＋LPA and DDP＋LPA＋PD98059 was assessed by methyl thiazolyl tetrazolium（MTT）.Cell apoptosis was detected by Hoechst33258.The expression of COX-2 in SKOV3 cells was assessed by RT-PCR.The apoptosis and cell cycle of SKOV3 cells were detected by flow cytometry（FCM）.Results：LPA could antagonize the inhibitory effect of DDP on the proliferation of SKOV3 cells,and increase the proportion of cells in the S phase of the cell cycle.However,PD98059 could significantly weaken these effect and increase apoptotic body.RT-PCR showed that LPA could increase the expression of COX-2 in SKOV3 cells（P0.05）,while PD98059 could decrease it（P0.05）.Conclusion：LPA may inhibit the apoptosis induced by DDP through MAPK signaling pathway.

关 键 词：溶血磷脂酸 卵巢肿瘤 MAPK信号传导通路 细胞凋亡 

分 类 号：R711.75[医药卫生—妇产科学]