Protective role of ABCG2 against oxidative stress in colorectal cancer and its potential underlying mechanism

Nie,Shuang; Huang,Yaqing; Shi,Mengyue; Qian,Xuetian; Li,Hongzhen; Peng,Chunyan; Kong,Bo; Zou,Xiaoping; Shen,Shanshan

doi:10.3892/or.2018.6594

Protective role of ABCG2 against oxidative stress in colorectal cancer and its potential underlying mechanism

Authors:
- Shuang Nie
- Yaqing Huang
- Mengyue Shi
- Xuetian Qian
- Hongzhen Li
- Chunyan Peng
- Bo Kong
- Xiaoping Zou
- Shanshan Shen
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Affiliations: Department of Gastroenterology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China, Department of Rheumatism and Immunology, Children's Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China
Published online on: July 24, 2018 https://doi.org/10.3892/or.2018.6594
Pages: 2137-2146

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Abstract

Colorectal cancer (CRC), one of the most common cancer types worldwide, is associated with a high mortality rate, and oxidative stress and inflammation play a vital role in this malignancy. A previous study by our group indicated that ATP binding cassette subfamily G member 2 (ABCG2) was capable of protecting cells from reactive oxygen species (ROS)‑mediated cell damage and death. In the present study, the role of ABCG2 in CRC was investigated by using clinical samples and cell lines. The levels of oxidative stress markers and inflammatory factors were increased, while the levels of antioxidants were decreased in CRC tissues or the serum of patients. Notably, high expression of ABCG2 in CRC tissues which may be the feedback of over-oxidative reaction, was associated with a poor prognosis. Further in vitro study indicated that the downregulation of ABCG2 induced ROS generation and inflammatory reactions, and inhibited the production of antioxidants. The nuclear factor (NF)-κB signaling pathway was activated under oxidative stress induced by ABCG2 knockdown. In conclusion, the present results indicated that ABCG2 may relieve oxidative stress and inflammatory response by inhibiting the NF-κB signaling pathway in cell models, and may thus play a potential protective role in CRC. This information may provide novel theoretical mechanisms and future targets for CRC therapy.

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