醛糖还原酶相似基因-1与人肝癌细胞药物敏感性的关系及相关基因的筛选

目的探讨醛糖还原酶相似基因-1（ARL-1基因）与人肝癌细胞药物敏感性的关系。及相关基因的筛选。方法线性化的ARL-1表达载体DNA转染至人肝癌细胞系（HepG-2细胞）。含有活性醛基的表阿霉素、丝裂霉索作为实验用药，不含活性醛基的5-氟尿嘧啶作为阳性对照。采用MTT法和流式细胞仪研究ARL-1基因对肝癌细胞耐药性的影响。并运用cDNA芯片技术对相关基因进行筛选。结果ARL-1基因成功转染至人肝癌细胞HepG-2后，加入含有活性醛基的表阿霉素和丝裂霉素后，实验组的细胞凋亡率明显低于对照组（P〈0．05）。耐药水平明显高于对照组。加入不含活性醛基的5-氟尿嘧啶后，两组的细胞凋亡率差异无统计学意义（P〉0.05）。cDNA芯片分析发现实验组8种基因的表达水平明显上调。9种基因的表达水平明显降低，涉及细胞的蛋白质代谢、信号传导、转移、耐药性等方面。结论转染ARL-1基因后，人肝癌细胞的耐药水平明显升高，而且基因的表达谱发生改变。为系统研究肝癌细胞的耐药性及其机制提供了有用的线索。

Relationship between aldose reductase-like-1 gene and drug sensitivity of human liver carcinoma cell and screening of the related genes by cDNA chips

Objective To study the effect of aldose reductase-like-1 gene on drug sensitivity of human liver carcinoma cell and screen related genes by cDNA chips.Methods The cultured human liver carcinoma cell(HepG-2) transfected by liner DNA vector of ARL-1 served as study group.E-ADM and MMC containing active aldehyde group were used as experimental drug,while 5-Fu no containing active aldehyde group as positive control drug.The role of ARL-1 in the drug resistance of the human liver carcinoma cell was studied by using MTT and flow cytometry.The related genes were screened by cDNA chips.Results After ARL-1 was transfected successfully,E-ADM and MMC were added separately,the apoptotic rate in study group was significantly lower than in control group((P<)(0.05),)and the level of drug resistance was enhanced greatly in study group.After addition of 5-Fu,there was no significant difference between two groups.cDNA chips showed that the expression of 6 kinds of genes was significantly up-regulated and that of 9 kinds of genes significantly down-regulated.Conclusion After transfection of ARL-1 gene,the level of drug resistance in liver carcinoma cell was enhanced significantly and gene expression profile was changed.