摘要
目的:探讨去甲基化药物5-杂氮-2'-脱氧胞苷(5-Aza-CdR)在裸鼠体内诱导HepG2细胞T-cadherin的表达,及其对HepG2种植瘤生长的抑制作用.方法:皮下接种法建立HepG2细胞裸鼠种植瘤模型,随机分为实验组(11只)和对照组(10只).实验组裸鼠给予5-Aza-CdR注射,对照组裸鼠注射等量PBS.4wk后处死裸鼠,观察种植瘤的生长情况,用RT-PCR技术及免疫组织化学技术检测T-cadherin mRNA及蛋白的表达.结果:用药4wk后,实验组肿瘤组织的T-cadherin mRNA的表达水平显著高于对照组(t=6.613,P<0.05);对照组HepG2细胞几乎检测不到T-cadherin蛋白表达,而实验组裸鼠种植瘤细胞膜上可检测到T-cadherin蛋白表达;实验组肿瘤的平均体积明显小于对照组肿瘤平均体积(t=2.337,P=0.025).结论:5-Aza-CdR能诱导裸鼠皮下种植HepG2瘤细胞的T-cadherin表达,抑制HepG2种植瘤的生长,其机制可能为5-Aza-CdR使甲基化的T-cadherin启动子去甲基化,恢复T-cadherin的表达,从而抑制HepG2种植瘤生长.
AIM： To observe 5-Aza-2＇-deoxycytidine （5-Aza- CdR）-induced T-cadherin gene expression in HepG2 cells and to determine its inhibitory effects on proliferation of HepG2-derived tumor cells in nude mice.
METHODS： The HepG2-derived tumor model in nude mice was established by subcutaneous inoculation. Twenty-one Nude mice were randomly divided into two groups： the experiment group （n = 11） and control group （n = 10）. Experiment group nude mice were intraperitoneally injected with 5-Aza-CdR while control group nude mice were only given equivalent volume of PBS. The mice were killed at week 4. Tumor growth in nude mice was observed, and the T-cadherin mRNA and protein expressions of the tumors were detected using reverse transcription-polymerase chain reaction （RT- PCR） and immunohistochemistry.
RESULTS： At the end of the fourth week, the T-cadherin mRNA expression in the tumors of the experiment group was significantly higher than that the control group （t = 6.613, P 〈 0.05）. Immunohistochemistry further showed that the protein expression of T-cadherin was almost not detected in the HepG2-derived tumor cells of the control group w while the T-cadherin expression was detected on the membranes of the HepG2-derived tumor cells of the experiment group. After 4 weeks＇ treatment with 5-Aza- CdR, the average volume of HepG2-derived tumors in the experiment group was significantly smaller than that in the control group （t = 2.337, P = 0.025）.
CONCLUSION： 5-Aza-CdR induces HepG2 cells to re-express T-cadherin and inhibits growth of HepG2-derived tumors in nude mice. Its mechanism may be that demethylation of the methylated T-cadherin promoter induced by 5-Aza-CdR restores T-cadherin reexpression and thus inhibits the growth of the HepG2-derived tumors in nude mice.
出处
《世界华人消化杂志》
CAS
北大核心
2008年第16期1741-1745,共5页
World Chinese Journal of Digestology
基金
国家自然科学基金资助项目
No.30471694
教育部新世纪优秀人才支持计划资助项目
No.NCET-04-0701~~
