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Aspirin promotes apoptosis in a murine model of colorectal cancer by mechanisms involving downregulation of IL-6-STAT3 signaling pathway.
- Source :
-
International Journal of Colorectal Disease . Jan2011, Vol. 26 Issue 1, p13-22. 10p. 1 Color Photograph, 5 Graphs. - Publication Year :
- 2011
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *COLON cancer
*ASPIRIN
*INTERLEUKIN-6
*CARCINOGENESIS
*ANIMAL models in research
Subjects
Details
- Language :
- English
- ISSN :
- 01791958
- Volume :
- 26
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- International Journal of Colorectal Disease
- Publication Type :
- Academic Journal
- Accession number :
- 56793048
- Full Text :
- https://doi.org/10.1007/s00384-010-1060-0