多药耐药白血病细胞中GCS基因高表达及其意义  

Higher expression and significance of glucosylceramide synthase in association with multidrug resistance of leukemia cells

作　　者：施媛萍[1] 谢平[2] 罗光华[1] 沈云志[3] 

机构地区：[1]苏州大学附属第三医院综合实验室,常州213003 [2]无锡市人民医院中心实验室 [3]苏州大学附属第三医院消化内科,常州213003

出　　处：《江苏医药》2009年第10期1196-1198,共3页Jiangsu Medical Journal

摘　　要：目的探讨葡萄糖神经酰胺合酶(GCS)基因在细胞株K562/AO2和K562中的表达与白血病多药耐药(MDR)的关系。方法RT-PCR技术检测K562/AO2及K562细胞株的GCS和Bcl-2基因的表达;ELISA法检测两细胞株中Bcl-2及Caspase-3的表达;AlamarBlueTM细胞染色法分析K562/AO2细胞经苯基棕榈酰胺吗啡丙醇(PPMP)处理后多药耐药性的变化。结果K562/AO2细胞的GCS基因、Bcl-2基因和Bcl-2蛋白表达明显强于K562细胞(P<0.01),Caspase-3则相反(P<0.05)。K562/AO2细胞经25μmol/LPPMP处理后,GCS基因表达抑制,阿霉素(ADR)对其半数抑制浓度(IC50)明显降低。结论GCS基因可能在白血病MDR形成过程中起着重要作用,其机制可能为细胞凋亡相关基因的表达异常。PPMP通过抑制GCS活性有效逆转K562/AO2细胞的多药耐药性。Objective To explore the relationship between the expression of glucosylceramide synthase （GCS） mRNA and multidrug resistance（MDR） in human leukemia cell strains. Methods Using RT-PCR technique,the expressions of GCS and Bcl-2 gene were detected in K562 and K562/ AO2 cell lines. ELISA was applied to detect Bcl-2 and Caspase-3 in the cells. Alamar BlueTM cell staining method was applied to analyze the change of MDR when K562/AO2 cells were treated by PPMP. Results Expressions of GCS and Bcl-2 gene of K562/AO2 ceils were higher than those of K562 ceils. K562/AO2 cells exhibited higher expression of Bcl-2 （P〈0. 01） and lower expression of Caspase-3 （P〈0.05）. The expression of GCS gene was inhibited and the IC50 of ADR was decreased after treated by PPMP at 25 μmol/L. Conclusion GCS gene might play an important role in MDR during human leukemia progression, which may be related to the abnormal expressions of the genes associated with cell apoptosis. PPMP can reverse MDR by inhibiting GCS gene expression in K562/ AO2 cell.

关 键 词：葡萄糖神经酰胺合酶基因 白血病细胞株 多药耐药 苯基棕榈酰胺吗啡丙醇 

分 类 号：R733[医药卫生—肿瘤]