5-Aza-CdR上调裸鼠胶质瘤SLC22A18基因的表达及其对胶质瘤的抑制作用  

5-Aza-2'-deoxycytidine-induced up-regulation of SLC22A18 expression in U251 cells gliomas and its inhibitory effects on the gliomas growth in nude mice

作　　者：楚胜华[1] 马延斌[1] 冯东福[1] 张红[1] 邱建华[1] 朱志安[1] 

机构地区：[1]上海交通大学医学院附属第三人民医院神经外科,201900

出　　处：《中国临床神经外科杂志》2011年第12期732-734,共3页Chinese Journal of Clinical Neurosurgery

基　　金：国家自然科学基金资助项目(NO:30901535);上海交通大学医学院"新百人计划"资助项目(NO:10XBR01)

摘　　要：目的探讨去甲基化药物5-杂氮-2’-脱氧胞苷(5-Aza-CdR)对胶质瘤U251细胞SLC22A18表达及对肿瘤生长的影响。方法皮下接种法建立胶质瘤U251细胞裸鼠种植瘤模型,随机分为实验组(12只)和对照组(12只)。实验组裸鼠皮下注射5-Aza-CdR,对照组裸鼠皮下注射等量PBS。4周后处死裸鼠,观察胶质瘤的生长情况,用逆转录PCR技术及免疫组织化学技术检测SLC22A18mRNA及蛋白的表达。结果用药4周后,对照组SLC22A18mRNA表达极低(0.132±0.056),而实验组表达明显增强(0.552±0.124),两者相差显著(P<0.01);对照组几乎检测不到SLC22A18蛋白表达,而实验组可检测到SLC22A18蛋白明显表达;用药4周后实验组肿瘤的体积为(982.52±415.45)mm3,对照组为(1468.56±642.34)mm3,两者相差显著(P<0.05)。结论 5-Aza-CdR能上调裸鼠皮下种植胶质瘤U251细胞的SLC22A18表达,抑制胶质瘤的生长,其机制可能为5-Aza-CdR使甲基化的SLC22A18启动子去甲基化表达,恢复SLC22A18的表达,从而抑制胶质瘤生长。Objective To explore the effect of 5-Aza-2＇-deoxycytidine （5-Aza-CdR） on SLC22A18 gene expression in U251 cell gliomas and proliferation of the gliomas in the nude mice. Methods Twenty-four nude mice with U251-derived gliomas induced by subcutaneous inoculation were randomly divided into two groups of 12 animals each, i.e. the experiment and control groups. The nude mice received subcutaneous injection of 5-Aza-CdR In the experiment group and equivalent volume of phosphate buffered solution in the control group. The mice were sacrificed 4 weeks after the first injection. The volume of the gliomas was determined. The SLC22A18 mRNA and protein expressions in the tumors were detected respectively by reverse transcription-polymerase chain reaction and immunohistochemical technique. Results The level （0.552 ± 0.124） of SLC22A18 mRNA expression in experiment group was significantly higher than that （0.132 ± 0.056） in the control group （P〈0.01）. The immunohistochemical technique showed that the expression of SLC22A18 protein was almost not detected in the control group and the expression of SLC22A18 protein was significantly detected in the experiment group. The volume [（982.52 ± 415.45） mm3] of U251-derived tumors in the experiment group was significantly smaller than that [（1468.56± 642.34）mm3] in the control group （P〈0.05）. Conclusion The up-regulation of SLC22A18 expression of glioma U251 cells may be induced by 5-Aza-CdR, which can inhibit the growth of U251 cell-derived gliomas in the nude mice via the demethylation of the methylated SLC22A 18 promoter and upregulation of SLC22A 18 expression induced by 5-Aza-CdR.

关 键 词：胶质瘤 U251细胞 SLC22A18基因 表达 5-杂氮-2’-脱氧胞苷 去甲基化 裸鼠 

分 类 号：R739.41[医药卫生—肿瘤] Q786[医药卫生—临床医学]