六氧甲基鸟嘌呤DNA甲基转移酶基因表达与肿瘤耐药  

O6-Methylguanine-DNA methyltransferase gene expression and chloroethylnitrosourea resistance in human tumor cell lines

作　　者：陈忠平[1] Mohr G Panasci LC 黄强[1] 

机构地区：[1]苏州医学院附二院脑外科

出　　处：《癌症》1998年第3期182-185,共4页Chinese Journal of Cancer

基　　金：美国NHI基金

摘　　要：目的：六氧甲基鸟嘌呤ＤＮＡ甲基转移酶（ＭＧＭＴ）能阻止由氮芥类导致的ＤＮＡ交连形成，因而降低其细胞毒性。本研究探讨肿瘤细胞对氯乙基亚硝脲（ＣＥＮＵ）耐药与其ＭＧＭＴ基因表达之间的关系。方法：采用ＲＮＡ印迹试验和蛋白印迹试验对１３株人肿瘤细胞的ＭＧＭＴ基因表达进行了检测，并与采用改良的ＳｕｌｆｏｒｈｏｄａｍｉｎａＢ（ＳＲＢ）比色抗癌药筛选法测定的肿瘤细胞对ＣＥＮＵ的耐药性进行比较。结果：肿瘤细胞ＭＧＭＴ的表达在ｍＲＮＡ水平和蛋白水平是一致的。ＭＧＭＴ阳性的肿瘤比ＭＧＭＴ阴性的肿瘤对ＢＣＮＵ（ｔ＝２．６１１，Ｐ＝０．０１）和ＳａｒＣＮＵ（ｔ＝２．５５８，Ｐ＝０．０１）明显耐药。可是，ＭＧＭＴ表达高低与肿瘤细胞耐药性程度之间无线性相关。结论：ＭＧＭＴ在肿瘤细胞对ＣＥＮＵ耐药中起重要作用，但除了ＭＧＭＴ之外，还有其它机制参与肿瘤耐药。Purpose: 06-methylguanine-DNA methyltransferase (MGMT) can provent the formation of DNA crosslink induced by nitrosoureas, so that the cytotoxicity of these reagents was reduced. This study is to investigate the relationship between chloroethylnitrosourea (CENU) resistance and MGMT expression in tumor cell lines. Methods: We evaluated MGMT gene expression utilizing Northern blot and Western blot analysis, and compared these results with CENU cytotoxicity as dertermined by a modified sulforhodamine B (SRB) colorimetric anticancer-drug screening assay, in 13 human tumor cell lines. Results: MGMT expression at mRNA level is in concordance with the protein level. MGMT positive cell lines are more resistant than MGMT negative cell lines to 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU)(t=2.611,P=0.01) and to 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU)(t=2.558,P=0.01). However, there was no linear correlation between MGMT expression and CENU cytotoxicity. Conclusions: Our results suggest that MGMT plays an important role in CENU resistance of human tumors, while mechanisms other than MGMT may also involving in drug resistance.

关 键 词：六氧甲基鸟嘌呤 药理学 肿瘤 耐药性 MGMT 

分 类 号：R963[医药卫生—微生物与生化药学] R730.53[医药卫生—药理学]