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.
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Acknowledgment
The authors thank Dr. Bing Guan (Jinling Hospital of Nanjing, China) for the excellent technical assistance in histologic assay.
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Tian, Y., Ye, Y., Gao, W. et al. Aspirin promotes apoptosis in a murine model of colorectal cancer by mechanisms involving downregulation of IL-6–STAT3 signaling pathway. Int J Colorectal Dis 26, 13–22 (2011). https://doi.org/10.1007/s00384-010-1060-0
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DOI: https://doi.org/10.1007/s00384-010-1060-0