神经元外单胺递质载体在人脑肿瘤的表达及其在SarCNU化疗中的意义

Extraneuronal Monoamine Transporter Expression in Human Brain Tumors and Its Significance in SarCNU Chemotherapy

目的 探讨神经元外单胺递质载体(EMT)在人脑肿瘤的表达与抗癌新药二氯乙基肌氨酰胺亚硝脲(SarCNU)敏感性之间的关系。方法 采用逆转录-聚合酶连锁反应(RT—PCR)测定EMT在人脑肿瘤细胞株和人脑肿瘤标本的表达,并与SarCNU细胞毒性试验结果进行相关性分析。结果检测的15株人脑肿瘤细胞都有不同程度的EMT表达,30例人脑肿瘤标本中25例EMT阳性。虽然单因素分析,肿瘤细胞EMT表达与SarCNU细胞毒性结果之间的相关性不显著。多元回归分析显示,SarCNU细胞毒性与EMT表达和六氧甲基鸟嘌呤DNA甲基转移酶(MGMT)、核苷酸切除修复系统的重要成员ERCC2表达显著相关(r=0.983,P=0.0001)。结论 脑肿瘤EMT和DNA修复基因表达与SarCNU的敏感性都有关。EMT阳性肿瘤将对SarCNU敏感,而大多数脑肿瘤有EMT表面,因此,SarCNU可望是理想的脑肿瘤化疗新药。

Objective To investigate extraneuronal monoamine transporter(EMT)gene expression in brain tumors and its significance in SarCNU chemotherapy. Methods EMT expression was determined by u-tilizing reverse - transcription polymerase chain reaction (RT- PCR) in 15 human brain tumor cell lines and 30 human brain tumor specimens. The results were correlated with SarCNU cytotoxicity in the cell lines. Results EMT was expressed in all 15 human brain tumor cell lines and in 25 out of 30 human brain tumor specimens. Although there was no significant correlation between SarCNU cytotoxicity and EMT expression by single factor analysis,multiple regression analysis demonstrated that the best correlation with SarCNU cytotoxicity was with EMT plus DNA repair protein, O6 - methylguanine - DNA methyltransferase(MGMT) and excision repair cross - complementing rodent repair deficiency gene 2 ( ERCC2) expression (r = 0. 983, P = 0.000 1).Conclusions This study suggests that both EMT and DNA repair factors, specifically, MGMT and ERCC2,are important determinants of SarCNU activity in human brain tumor cell lines. Since most of the human brain tumors are EMT positive,SarCNU should prove to be a useful chemotherapeutic agent for treatment of brain tumor.