结直肠癌发生过程中ABCG2与氧化应激水平的相关性及其机制探讨  

Correlation between ABCG2 and oxidative stress in the progress of colorectal cancer and its possible mechanism

作　　者：邵娜[1] 沈珊珊[1] 张斌[1] 黄淑玲[1] 邹晓平[1] 

机构地区：[1]南京大学医学院附属鼓楼医院消化科,210008

出　　处：《国际消化病杂志》2014年第6期396-400,共5页International Journal of Digestive Diseases

基　　金：国家青年自然科学基金项目(81201908);中央高校基本科研业务费-苗圃项目(1127021456);鼓楼医院青年启动基金(QJ2012004)

摘　　要：目的探讨结直肠癌(CRC)发生过程中ABCG2与氧化应激的相关性,并研究这一过程中可能涉及的NF-κB信号通路。方法 54例CRC患者及35名正常人的血清,54例CRC患者癌组织及相应正常肠黏膜标本均取自南京大学医学院附属鼓楼医院(2013年2月到2013年8月)。相关检测试剂盒分别检测标本中抗氧化应激标志物超氧化物歧化酶(SOD)和谷胱甘肽(GSH)水平,氧化应激标志物脂质过氧化产物丙二醛(MDA)和DNA氧化损伤产物8-羟基脱氧鸟苷(8-OHdG)水平。酶联免疫吸附法(ELISA)检测肿瘤坏死因子-α(TNF-α)和白细胞介素-8(IL-8)水平。蛋白免疫印迹法检测组织中ABCG2和核因子-κB(NF-κB)蛋白表达水平。结果与正常对照组相比,CRC患者血清中SOD和GSH水平下降(P<0.01),MDA和8-OHdG增加(P<0.05);CRC患者组织中SOD水平下降(P<0.01),8-OHdG水平升高(P<0.05);CRC患者组织中NF-κB、炎性反应因子TNF-α及IL-8水平升高(P<0.05),ABCG2水平下降(P<0.01)。相关性分析显示,ABCG2、抗氧化应激标志物及氧化应激标志物、NF-κB的水平之间存在一定的相关性(P<0.05)。结论 ABCG2表达水平下降可能使有毒物质、炎性反应因子等在肠黏膜累积,导致氧化应激,进而促进CRC发生。此外,NF-κB信号通路可能参与调控CRC的氧化应激水平,其机制有待进一步研究证实。Objective This paper investigated the correlation between ATP-binding cassette family G2 transporters （ABCG2）and oxidative stress in the progress of human colorectal cancer and its possible mechanism in this procedure. Methods The serums from 54 colorectal cancer patients,35 normal controls and tissues from 54 colorectal cancer patients,54 correspondent normal controls were collected from the Affiliated Drum Tower Hospital of Medical School,Nanjing University （from Feb.2013 to Aug.2013）.Related kits were used to estimate the antioxidants such as superoxide dismutase （SOD）and glutathione （GSH）,the product of lipid peroxidation as malondialdehyde （MDA）,and biomarker of oxidative injury of DNA as 8-hydroxydeoxyguanosine （8-OHdG）respectively.Tumor necrosis factor （TNF-α）and interleukin-8 （IL-8）were detected by enzyme-linked immunosorbent assay. Western-blotting was applied to determine the expressions of ABCG2 and nuclear factor-κB （NF-κB）.Results Statistically significant lower values of antioxidants SOD and GSH were observed in colorectal cancer patients′serums （P 〈0.01）,while the mean level of the products of oxidative stress as MDA and 8-OHdG in colorectal cancer patients′serums was higher than that in normal controls （P 〈 0.05 ）.The value of antioxidants SOD was lower in colorectal cancer patients′tissues （P 〈0.01）,where as the level of MDA which was the product of oxidative stress was higher in colorectal cancer patients′tissues （P 〈0.05 ）.There were significant increased levels of NF-κB and inflammatory factors （TNF-αand IL-8）in colorectal cancer patients′tissuses （P 〈0.05）,while the level of ABCG2 was reduced in the cancer group （P 〈0.01）.ABCG2,the level of antioxidants,products of oxidative stress and NF-κB were related to each other by correlation analysis （P 〈0.05）.Conclusion The deficiency of ABCG2 in local intestinal epithelial tissue may lead to the accumulation of toxic substances,such as inflammation fact

关 键 词：结直肠癌 ABCG2 转运子 氧化应激 核因子-ΚB 

分 类 号：R735.34[医药卫生—肿瘤]