期刊
BIOCHEMICAL PHARMACOLOGY
卷 115, 期 -, 页码 51-63出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2016.06.004
关键词
Hydroxychloroquine; Colitis-associated colorectal cancer; Macrophages; Toll-like receptor 4; Reactive oxygen species
资金
- National Natural Science Foundation of China [81272593, 81572592, 81372621]
- Key Projects of Natural Foundation of Zhejiang Province [LZ15H160001]
- National Health and Family Planning Commission Fund [2015112271]
- Zhejiang Province Preeminence Youth Fund [LR16H160001]
Chronic inflammation in the intestine is a strong risk factor for colitis-associated colorectal cancer (CAC). Hydroxychloroquine (HCQ) is widely used as an anti-inflammatory drug in the treatment of immune mediated inflammatory disorders and various tumors. However, little is known regarding the effects of HCQ on colitis-associated tumorigenesis. In this study, mice treated with HCQ showed a significant reduction in early-stage colitis following azoxymethane (AOM)/dextran sodium sulfate (DSS) administration, as well as a remarkable inhibition of colonic tumorigenesis and tumor growth at late stages of CAC. Mechanistically, the therapeutic effects of HCQ were attributed to inhibition of inflammatory responses and production of mutagenic reactive oxygen species (ROS) in immune cells and subsequent promotion of apoptosis and cell cycle arrest in tumor cells. Furthermore, we found that HCQ inhibited the production of inflammatory cytokines and ROS in response to toll-like receptor 4 (TLR4) activation in macrophages. Our data presented herein may help guide the clinical use of HCQ as a prevention and treatment strategy for CAC. (C) 2016 Elsevier Inc. All rights reserved.
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