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Aspirin promotes apoptosis in a murine model of colorectal cancer by mechanisms involving downregulation of IL-6–STAT3 signaling pathway

International Journal of Colorectal Disease volume 26, pages 13–22 (2011)Cite this article

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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Affiliations

  1. Cancer Research Institute, the First Affiliated Hospital, China Medical University, Shenyang, 110001, China

    Yun Tian, Hong Chen, Daqing Wang & Changshan Ren

  2. Department of Anesthesiology, the First Affiliated Hospital, China Medical University, Shenyang, 110001, China

    Ying Ye

  3. Department of Respiratory Diseases, Jinling Hospital, Medicine School of Nanjing University, Nanjing, 210002, China

    Wei Gao

  4. The Fourth Department of Infectious Diseases, Qingdao Infectious Disease Hospital, Qingdao, 266033, China

    Ting Song

  5. Department of Surgical Oncology, the First Affiliated Hospital, China Medical University, Shenyang, 110001, China

    Xiaoyun Mao

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  1. Yun Tian
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  2. Ying Ye
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  3. Wei Gao
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  4. Hong Chen
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  5. Ting Song
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  8. Changshan Ren
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Correspondence to Changshan Ren.

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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

Keywords

  • Colorectal cancer
  • Aspirin
  • IL-6
  • STAT3
  • Apoptosis