The Correlation Of ABCG2 And Oxidative Stress In Colorectal Cancer And Its Possible Mechanism

Aims:Colorectal cancer (CRC) is one of the most common human malignancy, its incidence is rising year by year in our country. The accumulation of reactive oxygen species (ROS) and its related metabolic product in the process of oxidative stress could produce a variety of toxic effects, and induce the occurrence of cancer. The nucleus factor-kB (NF-κB) is the earliest discovered transcription factor related to cellular redox status. Studies confirm that oxidative stress can active the NF-κB, leading to many diseases including CRC.ABCG2 transporter is a membrane transporter encoded by ABC gene families, plays an important role in intestinal barrier of defense, studies found ABCG2 had the ability of antioxidant, and preliminarily confirmed in colon cancer cells. In this study we will explore the relationship of ABCG2 and oxidative stress in colorectal cancer from human serums and tissues, and the NF-κB cell signaling pathway which may be participated in this procedure. In order to providing a valuable target and theoretical basis for CRC.Metholds:(1)Sample Collection. Serums and tissues from normal controls, colorectal precancerous lesion and colorectal cancer patients were collected from the Affiliated Drum Tower Hospital of Nanjing University Medical School (2013/02--2013/08). (2)The level of oxidative stress in CRC.Related kits were used to estimate the antioxidants such as superoxide dismutase(SOD) and glutathione(GSH), detect the product of lipid peroxidation as malondialdehyde(MDA), biomarker of oxidative injury of DNA as 8-hydroxydeoxyguanosine(8-OHdG) respectively.(3)Detection of inflammatory cytokines. Tumor necrosis factor (TNF-a) and interleukin-8(IL-8) were detected by enzyme-linked immunosorbent assay. (4)Western blotting was applied to determine the expressions of ABCG2 and NF-κB.Results:(1) Statistically significantly lower values of SOD in serums were observed in colorectal cancer patients compared with normal controls and colorectal precancerous lesion(P<0.01,P<0.05), the values of GSH in colorectal cancer patients were lower than in normal controls and colorectal precancerous lesion(P< 0.01,P<0.01). MDA which is the product of lipid peroxidation was found higher in colorectal precancerous lesion and colorectal cancer than in normal controls (P< 0.01, P<0.05),mean level of 8-OHdG which is a biomarker of oxidative injury of DNA in colorectal precancerous lesion was higher than in normal controls (P<0.05). (2)Lower values of SOD in tissues were observed in colorectal cancer patients compared with normal controls and colorectal precancerous lesion (P<0.05, P< 0.01),the level of SOD in precancerous lesion was higher than in normal controls (P <0.01),GSH in tissues can not be detected, values of MDA in different tissues have no significant difference, mean level of 8-OHdG in tissues which collected from colorectal cancer patients was higher than those from colorectal precancerous lesion (P<0.01), while 8-OHdG reduced significantly in precancerous lesions compared with normal control.(P<0.01). (3)There was a increased level of TNF-a in colorectal cancer in contrast to normal controls and colorectal precancerous lesion (P<0.05,P <0.05),the variation of IL-8 was similar to TNF-a (P<0.01, P<0.01).(4) NF-κB in tissues increased along with the development (P< 0.01), while ABCG2 reduced in the carcinogenesis gradually (P<0.01).(5)Correlation analysis found that MDA had a positive correlation with 8-OHdG (r=0.510, P=0.018), SOD had a negative correlation with TNF-a (r=-0.569, P=0.034),8-OHdG had a positive correlation with IL-8 (r=0.525, P=0.044), ABCG2 had a negative correlation with SOD (r=-0.518, P=0.040),ABCG2 had a negative correlation with NF-κB (r=-0.503, P=0.047)Conclusions:In the process of the occurrence of colorectal cancer, the expression of ABCG2 was decreased, while the level of oxidative stress and the expression of inflammatory cytokines were increased. ABCG2 had a high expression in normal intestinal epithelial to protect the intestinal epithelium from toxic substances. Deficiency of ABCG2 in intestinal mucosa will lead to the accumulation of toxic substances and inflammation factors, leading to increase the level of oxidative stress. NF-κB signaling pathways could regulate gene transcription in this procedure to induce the occurrence of CRC. Oxidative stress is closely related to CRC, but the specific mechanism is still not very clear and needs to be further researched.