醛糖还原酶相似基因-1与人肝癌细胞耐药性关系的实验研究

目的探讨醛糖还原酶相似基因-1（ARL-1基因）与人肝癌细胞耐药性的关系。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）作为实验组。含有活性醛基的表阿霉素、丝裂霉素作为实验用药，不含活性醛基的氟尿嘧啶作为阳性对照。通过乳酸脱氢酶（LDH）的测定、MTT法和流式细胞仪研究ARL-1基因在肝癌细胞耐药性形成中的作用。结果ARL-1基因成功转染至人肝癌细胞HepG-2，加入表阿霉素和丝裂霉素后，实验组的细胞毒性水平和细胞凋亡率明显低于对照组（P〈0．05），耐药水平明显上升。加入氟尿嘧啶后，实验组及对照组的耐药水平无明显差异。结论高表达的ARL-1基因明显降低含有活性醛基化疗药物的细胞毒性和抑制其所诱导的细胞凋亡，增强人肝癌细胞的耐药性。

Relationship between aldose reductase-like-1 gene and drug resistance in human liver carcinoma cells

Objective To investigate the relationship between aldose reductase-like-1 (ARL-1) gene and drug resistance in human liver carcinoma cells. Methods The human liver carcinoma cell line HepG-2 transfected by linear DNA vector of ARL-1 was used for the study. E-ADM and MMC containing active aldehyde were used for the experimental group and 5-Fu not containing active aldehyde was used for the positive control group. The role of ARL-1 in the drug resistance of human liver carcinoma cells was determined through detection of L-lactate dehydrogenase, MTT and flow cytometry. Results ARL-1 was successfully transfected. When E-ADM and MMC were added, the cytotoxicity and cell apoptotic rate were significantly lower in the experimental group than that in the control group (P<0.05). Meanwhile, the drug resistance was greatly enhanced in the experimental group. However, there was no significant difference between the 2 groups after addition of 5-Fu. Conclusions High level of ARL-1 gene expression can significantly suppress the cytotoxicity and reducer the cell apoptosis induced by chemotherapeutic drugs containing active aldehyde. Meanwhile, it can enhance the drug resistance.