神经元外单胺递质载体和DNA修复rn基因表达与SarCNU在荷人肿瘤裸鼠rn的抗肿瘤作用

摘要

Objective　To clarify if there ar e any correlations between extraneuronal monoamine transmitters (EMT), DNA repa ir gene expressions and SarCNU antitumor efficacy. Methods　EMT, DNA repair gene O6-methylguanine-DNA methyltransferase (M GMT) and excision repair cross-complementing rodent repair deficiency gene (ERC C1～6) expressions in 9 human xenograft tumor models were determined by RT-P CR. The results were compared with the antitumor effects of SarCNU on these tumo r xenografts. Results　Multiple regression a nalysis revealed significant correlations of SarCNU antitumor activity with dif ferent combinations of gene expression. The most significant correlation was o bserved with all of the 4 genes expressed. Conclusion　The results suggest that expression of both EMT and DNA repair genes, specifically, MGMT, ERCC2 and ERCC4, are important determinants of SarCNU activ ity against human tumors. While DNA repair decreases SarCNU′s activity by repa iring damaged DNA, EMT appears to enhance its antitumor efficacy.%目的探讨抗癌新药肌氨酰胺亚硝脲(SarCNU)在体内的抗肿瘤作用是否与神经元外单胺递质载体和DNA修复基因表达相关。方法采用逆转录-聚合酶连锁反应(RT-PCR)，测定了9个人肿瘤动物模型的肿瘤神经元外单胺递质载体(EMT)和DNA修复基因六氧甲基鸟嘌呤DNA甲基转移酶(O 6-methylguanine-DNA methyltransferase, MGMT)、核苷酸切除修复基因ERCC1-6的表达，并与rnSarCNU在荷人肿瘤的裸鼠的抗肿瘤作用进行相关性分析。结果多元回归分析发现，EMT、MGMT、ERCC2和ERCC4的不同组合，与SarCNU治疗效果间有相关性。而且，综合全部4个因素(EMT、MGMT、ERCC2和ERCC4)，其与SarCNU治疗效果的相关性最显著(r=0.961,P=0.017)。结论 Sar CNU的抗肿瘤作用与肿瘤是否表达EMT和DNA修复基因有关，即：EMT阳性的肿瘤对SarCNU 敏感；但若同时具有DNA修复基因，如MGMT、ERCC2、ERCC4的表达，则其敏感性下降。