反义mdr1对鼻咽癌细胞放射敏感性的影响

Effect of inhibiting mdr1 on radiosensitivity in nasopharyngeal carcinoma cell line

目的:探讨用反义技术抑制多药耐药基因1(Multidrug resistance gene 1,mdr1基因)对鼻咽癌细胞CNE放射敏感性的影响。方法:设立空白组、脂质体组(仅加入等量的脂质体)和mdr1正义寡核苷酸组作对照,用RT-PCR检测鼻咽癌细胞转染反义mdr1前后mdr1表达水平的变化。用集落形成试验检测各实验组照射后人鼻咽癌CNE细胞株的集落形成率,免疫组织化学法测定甲基鸟嘌呤甲基转移酶(Methylguanine-methyltransferase,MGMT)的表达。结果:mdr1反义寡核苷酸能有效抑制mdr1基因的表达。mdr1反义寡核苷酸+60Coγ射线照射组,其集落形成率较正义寡核苷酸组及单纯照射组明显下降,MGMT蛋白的表达也显著下调,与各对照组比较有显著差异(P<0.05)。结论:mdr1反义寡核苷酸通过抑制mdr1基因降低了人鼻咽癌CNE细胞放射抗性。其辐射增敏作用可能与mdr1反义寡核苷酸下调照射后鼻咽癌细胞MGMT蛋白表达有关。

Objective：To explore the effect of inhibiting mdrl by antisense technology on radiosensitivity in nasopharyngeal carcinoma cell line（CNE ）. Methods：There were four groups in the study：control group, lipofectin group, sense oligodexynucleotides （SODN） group,and antisense oligodexynucleotides（ASODN） group. The expression of mdrl was detected by RT-PCR. Cellular response to irradiation was evaluated by the colony forming test. Methylguanine-DNA methyltransferase（MGMT）protein expression was determined by immunohistochemical staining. Results：ASODN group could significantly decrease the proliferation rate and downregulate the expression of MGMT of irradiated nasopharyngeal carcinoma cells（vs lipofectin group or SODN group,P〈0.05）. Conclusion..mdrl antisense oligodexynucleotides sensitize the CNE to ionizing irradiation through decreasing the expression of mdrl,which might be related to decreasing the expression of MGMT.