锰卟啉光动力学疗法对人膀胱癌BIU-87细胞Bcl-2表达的影响  

Effect of Photodynamic Therapy with Manganese Metalloporphyrin on Bcl-2 Expression in Human Bladder Cancer Cell Line BIU-87

作　　者：曹正国[1] 诸禹平[1] 孙友文[1] 贾涛[2] 舒启安[1] 苏红[1] 

机构地区：[1]安徽医科大学附属省立医院,安徽合肥230001 [2]武汉大学药学院,湖北武汉430070

出　　处：《中国肿瘤》2008年第3期239-242,共4页China Cancer

基　　金：安徽省自然科学基金(070413071);安徽省高校省级自然科学研究项目(KJ2007B194)

摘　　要：[目的]研究锰卟啉的光动力学疗法(PDT)对人膀胱癌BIU-87细胞Bcl-2表达的影响,探讨其诱导BIU-87细胞凋亡的机制。[方法]合成水溶性金属卟啉化合物5,10,15,20-四(N-甲基-4-吡啶基)锰卟啉四碘盐(锰卟啉)后,分别采用膜联蛋白(Annexin-Ⅴ)/碘化丙锭(PI)双标记流式细胞术、逆转录聚合酶链反应(RT-PCR)和Western-blotting检测锰卟啉在不同时间(0、10、20、30min)的PDT对人膀胱癌BIU-87细胞的凋亡率和Bcl-2mRNA及其蛋白质表达水平的影响。[结果]1μmol/L锰卟啉的PDT作用20min和30min后均能诱导BIU-87细胞凋亡,凋亡率分别为9.08%±1.55%、19.15%±2.39%;在诱导细胞凋亡过程中,锰卟啉的PDT能显著抑制BIU-87细胞中Bcl-2mRNA和相应蛋白质的表达,且锰卟啉的PDT作用对细胞凋亡和Bcl-2表达的影响有显著的光照剂量依赖性。[结论]适宜光照剂量锰卟啉的PDT可以通过抑制凋亡抑制基因Bcl-2的表达来诱导BIU-87细胞发生凋亡,为金属卟啉PDT的临床应用提供了实验依据。[Purpose] To investigate the effect of photodynamic therapy（PDT） with manganese metalloporphyrin on Bcl-2 expression in human bladder cancer cell line BIU-87 in vitro,and to explore the mechanism of PDT induced BIU-87 cells apoptosis. [Methods] A composition of water-soluble metalloporphyrin [5,10,15,20-tetra （N-methyl-4-pyridyl） porphinato （2-）] and tetraiodide salt （manganese metalloporphyrin） was made. BIU-87 cells were treated with the PDT with manganese metalloporphyrin. The Annexin-Ⅴ/PI double-labeled flowing cytometry technique,semi-quantitive reverse transcription polymerase chain reaction （RT-PCR） and Western-blotting technique were used to detect the apoptotic rate,expression of Bcl-2 mRNA at different time （0,10,20,30 min） respectively. [Results] The effects of PDT with 1μmol/L manganese metalloporphyrin reacted for 20 and 30 min both could induce BIU-87 cells apoptosis and the apoptotic rate of BIU-87 cells were 9.08%±1.55% and 19.15%±2.39%,respectively. During the PDT induced cells apoptosis process,PDT with manganese metalloporphyrin significantly inhibited the Bcl-2 mRNA expression and its protein in BIU-87 cells. The effects of PDT with manganese metalloporphyrin on the apoptosis and Bcl-2 expression of significantly correlated to the dose of photodynamic time. [Conclusion] PDT with manganese metalloporphyrin in certain photodynamic dose can induce BIU-87 cells apoptosis by down-regulating the Bcl-2 expression of apoptosis inhibition gene,which provides the experimental evidence for clinical application of PDT.

关 键 词：金属卟啉 光动力疗法 膀胱肿瘤 Bcl-2 凋亡 

分 类 号：R73-36[医药卫生—肿瘤] R737.4[医药卫生—临床医学]