摘要
目的探讨核因子E2p45相关因子2(Nrf2)在表没食子儿茶素没食子酸酯(EGCG)对结肠原位种植肿瘤中诱导尿苷二磷酸葡萄糖醛酸转移酶(UGT)及其同工酶表达中的作用机制。方法运用RNAi技术建立Nrf2基因低表达的结肠癌细胞系HT-29,常规培养至对数生长期,在BALB/cA裸小鼠中建立皮下肿瘤模型,用皮下肿瘤构建裸鼠结肠原位肿瘤模型。分别用低、中、高剂量EGCG作用4周,实验结束后,剥离结肠原位肿瘤组织,用免疫组化检测其中Nrf2蛋白表达和RT-PCR法检测Nrf2、UGT1A、UGT1A8和UGT1A10基因的mRNA表达水平。结果与对照组比较,不同剂量EGCG组的动物体质量、对肿瘤生长的抑制率和Nrf2的蛋白水平均无显著性差异,Nrf2、UGT1A、UGT1A8和UGT1A10的mRNA水平无显著性差异。结论 Nrf2在EGCG诱导裸鼠结肠原位种植肿瘤UGT1A及其同工酶的表达中发挥着重要作用。
Objective To investigate the role of nuclear factor NF-E2-related factor 2（Nrf2） in the expression of UDP-glucuronosyltransferase（UGT1A） and its isoforms induced by epigallocatechin gallate（EGCG） in colon cancer.Methods We used the technology of RNA interference to block the expression of Nrf2 in HT-29 cell line and cultivated the cell line to the phase of logarithmic growth.Using HT-29-siNrf2 cell line we constructed subcutaneous cancer model in the BALB/cA nude mice.Using subcutaneous tumor we constructed orthotopic colon cancer model in nude mice.After been administrated with low-,medium-and high-dose of EGCG for 4 weeks,the orthotopic colon cancer was peeled.The protein expression of Nrf2 of colon cancer was detected by IHC and the mRNA levels of Nrf2,UGT1A,UGT1A8 and UGT1A10 were detected by RT-PCR.Results The body weights of the mice,the inhibition rate of orthotopic colon cancer and the protein expression of Nrf2 detected by IHC had no significant difference as compared with mice in model group.The mRNA levels of Nrf2,UGT1A,UGT1A8 and UGT1A10 detected by RT-PCR had no significant difference.Conclusion Nrf2 plays a critical role in the expres-sion of UGT1A and its isforms induced by EGCG.
出处
《基础医学与临床》
CSCD
北大核心
2010年第12期1257-1262,共6页
Basic and Clinical Medicine
基金
国家自然科学基金(30370634)
