5-氮-2′-脱氧胞苷对人子宫内膜癌裸鼠移植瘤的p16基因去甲基化抑瘤作用  

Growth Inhibition Effect of 5-aza-CdR on Endometrial Carcinoma Xenografted in Nude Mice by p16 Gene Demethylation

作　　者：晁红霞[1] 孙建衡[1] 陆士新[2] 王月英[2] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤医院妇科,北京100021 [2]中国医学科学院中国协和医科大学肿瘤医院肿瘤病因研究室,北京100021

出　　处：《中华妇产科杂志》2000年第4期229-232,共4页Chinese Journal of Obstetrics and Gynecology

摘　　要：目的　研究 5 氮 2′ 脱氧胞苷 (5 aza CdR)对人子宫内膜癌裸鼠移植瘤的作用 ,探讨其抗肿瘤效应及可能机理。方法　用人子宫内膜癌裸鼠移植瘤模型 (SL I) ,观察 5 aza CdR对其抗肿瘤作用。根据用药不同分为 5 aza CdR组、5 aza CdR +顺铂 (DDP)组、DDP组和对照组 (注入生理盐水 ) ,测定用药前后各组肿瘤体积的变化 ;采用限制性内切酶酶切、聚合酶链反应 (PCR)及逆转录 聚合酶链反应 (RT PCR)检测裸鼠移植瘤用药前后p16基因 5′二核苷酸胞嘧啶 (CpG)岛甲基化状态及p16基因mRNA表达水平的改变。结果　 5 aza CdR组、5 aza CdR +DDP组及DDP组与对照组比较 ,其抑瘤率分别为 79.10 %、90 .32 %及 10 .13% ,前两组分别与对照组比较 ,差异均有极显著性 (P <0 .0 1) ,DDP组与对照组比较 ,差异无显著性 (P >0 .0 5 )。用 5 aza CdR后 ,SL I的p16基因甲基化水平逐渐降低 ,mRNA表达逐渐恢复。结论　 5 aza CdR有肯定的抑瘤作用 ,其抑瘤作用的可能机理主要是通过p16基因去甲基化解除转录抑制完成的。Objective To study the antitumor effect and mechanism of 5 aza CdR on endometrial carcinoma xenografted in nude mice. Methods The effects of 5 aza CdR on tumor growth inhibition were observed on human endometrial carcinoma xenografted in nude mice. The methylation status of the 5′ CpG island of the p16 gene was evaluated using methylation sensitive restriction enzymes and polymerase chain reaction. p16 mRNA expression was determined by reverse transcription polymerase chain reaction. Results The inhibition rates of the tumor were 79.10% in 5 aza CdR group ( P <0.01), 90.32% in 5 aza CdR+DDP group ( P <0.01), and 10.13% in DDP group ( P >0.05), respectively, in comparison with control group. The methylation level of p16 gene was gradually decreased and the p16 mRNA expression restored after exposure to 5 aza CdR. Conclusion Our data show that 5 aza CdR may inhibit tumor growth by reactivating growth regulatory genes silenced by de novo methylation.

关 键 词：阿扎胞苷 子宫内膜肿瘤 小鼠 裸 基因 p16 

分 类 号：R737.33[医药卫生—肿瘤]