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Aspirin promotes apoptosis in a murine model of colorectal cancer by mechanisms involving downregulation of IL-6-STAT3 signaling pathway.
MedLine Citation:
PMID:  20886344     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
BACKGROUND AND AIMS: Aspirin is associated with a reduced risk of colorectal cancer (CRC), and it showed inhibited effects on interleukin 6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway which is thought to play an important role in intestinal inflammation and the tumorigenesis of CRC.
METHODS: Mouse model for inflammation-related CRC was induced by a combined treatment with azoxymethane (AOM) and dextran sodium sulfate (DSS) in BALB/c mice. Effects of aspirin on tumor number and size and apoptosis of CRC cells were investigated. Key molecules of IL-6-STAT3 pathway, such as IL-6, sIL-6R, phosphorylated STAT3, and their downstream anti-apoptotic genes Bcl-2 and Bcl-xl, were assessed by ELISA and Western blot.
RESULTS: Treatment with aspirin significantly promoted CRC cell apoptosis in AOM/DSS-induced CRC mice in vivo. The expression level of IL-6, which is an upstream molecule of STAT3 and capable of activating STAT3, was reduced in aspirin-treated mice. Furthermore, the phosphorylated form of STAT3 and the levels of STAT3's target gene products such as Bcl-xl and Bcl-2, which are essential for cell growth and survival, were also decreased in aspirin-treated mice.
CONCLUSIONS: Our data suggested that the protective mechanisms of aspirin in CRC may be associated with its effects on induction of CRC cell apoptosis and suppression of IL-6-STAT3 signaling pathway, which implied that aspirin has a potential therapeutic activity in CRC.
Authors:
Yun Tian; Ying Ye; Wei Gao; Hong Chen; Ting Song; Daqing Wang; Xiaoyun Mao; Changshan Ren
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Publication Detail:
Type:  Journal Article     Date:  2010-10-01
Journal Detail:
Title:  International journal of colorectal disease     Volume:  26     ISSN:  1432-1262     ISO Abbreviation:  Int J Colorectal Dis     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607899     Medline TA:  Int J Colorectal Dis     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  13-22     Citation Subset:  IM    
Affiliation:
Cancer Research Institute, the First Affiliated Hospital, China Medical University, Shenyang 110001, China.
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