表没食子儿茶素没食子酸酯对结肠肿瘤生长与转移的作用  

Effects of epigallocatechin gallate on growth and metastases of colonic cancer

作　　者：袁俊华[1] 姜虹[1] 杨晓云[2] 李延青[3] 

机构地区：[1]山东大学附属省立医院保健消化科,济南250021 [2]山东大学齐鲁医院查体中心 [3]山东大学齐鲁医院消化科

出　　处：《中华消化杂志》2010年第1期18-23,共6页Chinese Journal of Digestion

基　　金：国家自然科学基金资助项目（30370634）

摘　　要：目的观察不同浓度表没食子儿茶素没食子酸酯（epigallocatechin gallate, EGCG）对结肠肿瘤原位生长与转移的作用。方法将40只BALB／C裸鼠均分为对照组和低、中、高剂量组。除对照组外，其他3组分别给予低、中或高浓度EGCG（分别为5、10和20mg·kg^-1·d^-1），观察对结肠原位种植肿瘤的生长和转移的影响。HE染色观察肝、肺组织病理学改变；免疫组化检测结肠肿瘤组织中核因子E2p45相关因子2（NF—E2-related factor 2,Nrf2）基因的蛋白表达水平；RT—PCR检测Nrf2、尿苷二磷酸葡萄糖醛酸基转移酶（UGT）1A、UGT1A8和UGT1A10基因的mRNA表达水平。结果低、中、高剂量EGCG组裸鼠肿瘤的平均重量为（152±63）、（76±42）和（18±10）mg，与对照组[（564±130）mg]比较差异有统计学意义（P值均〈0．05）。3组的肿瘤抑制率分别是73．0％、86．5％和96．8％。EGCG对肿瘤生长的抑制率与EGCG的刹量呈正相关（P值均〈0．05）。不同剂量EGCG组Nrf2基因的蛋白表达水平明显高于对照组（P〈0．05），且有核转录现象。不同剂量EGCG组Nrf2、UGT1A、UGT1A8和UGT1A10基因的mRNA表达水平明显高于对照组（P〈0．05）。结论不同浓度的EGCG能预防裸鼠HT29结肠原位肿瘤的局部生长和远处转移，且有剂量依赖效应。这种作用可能通过诱导Nrf2、UGT1A、UGT1A8和UGTIA10基因的表达起作用。Objective To investigate the preventive effects of epigallocatechin gallate （EGCG） on growth and metastases of orthotropic colonic cancer. Methods Forty BALB/C male nude mice were prepared for model of colonic cancer and then divided into control group and low- , medium- and high-dose of EGCG groups with 10 each. Except control group, the mice in other three groups were treated with 5, 10 and 20 mg·kg^-1·d^-1 of EGCG. The effect of EGCG on growth and metastases of colonic cancer was observed. The histopathologic changes of liver and lung were observed with HE, and protein expression of NF-E2 related factor 2 （Nrf2） in cancerous tissue was detected by immunohistochemistry. RT-PCR was used to examine mRNA levels of Nrf2, UDP-glucuronosyltrans- ferase （UGT）IA, UGT1A8 and UGT1A10. Results In comparison with control group [（564±130） mg], the average weight of the tumor in low-, medium- and high dose groups was （152±63）mg, （76±42） mg and （18±10）mg, respectively, with tumor inhibitory rate of 73. 0%, 86. 5% and 96.8%, respectively （all P value〈0.05）. There was a positive correlation between tumor inhibitory effect and dosage of EGCG （P〈0.05）. The protein expression of Nrf2 and the mRNA levels of Nrf2, UGT1A, UGT1A8 and UGT1A10 in three EGCG treated groups were increased significantly compared with control group （P〈0. 05）. and there was a phenomenon of nuclear transcription of Nrf2. Conclusions EGCG can prevent local growth and metastases of orthotopic colonic cancer in a dose dependent manner in nude mice. The inhibitory effect may be caused by inducing the expressions of Nrf2, UGT1A, UGT1A8 and UGT1A10 genes.

关 键 词：结肠肿瘤 表没食子儿茶素没食子酸酯 NF—E2相关因子2 葡萄糖醛酸转移酶 

分 类 号：R285.5[医药卫生—中药学]