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

Expression of extraneuronal monoamine transporter gene and DNA repair gene visàvis with antitumor efficacy of SarCNU in human tumor xenografts

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 (O6 methylguanine DNAmethyltransferase ,MGMT)、核苷酸切除修复基因ERCC1 6的表达 ,并与SarCNU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 96 1,P =0 0 17)。结论 SarC NU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。

Objective To clarify if there are any correlations between extraneuronal monoamine transmitters (EMT), DNA repair gene expressions and SarCNU antitumor efficacy. Methods[WT5”BZ] EMT, DNA repair gene O 6methylguanineDNA methyltransferase (MGMT) and excision repair crosscomplementing rodent repair deficiency gene (ERCC1～6) expressions in 9 human xenograft tumor models were determined by RTPCR. The results were compared with the antitumor effects of SarCNU on these tumor xenografts. Results Multiple regression analysis revealed significant correlations of SarCNU antitumor activity with different combinations of gene expression. The most significant correlation was observed with all of the 4 genes expressed. Conclusion[WT5”BZ] The results suggest that expression of both EMT and DNA repair genes, specifically, MGMT, ERCC2 and ERCC4, are important determinants of SarCNU activity against human tumors. While DNA repair decreases SarCNU′s activity by repairing damaged DNA, EMT appears to enhance its antitumor efficacy.