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International Journal of Colorectal Disease

Published in:

01-01-2011 | Original Article

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

Authors: Yun Tian, Ying Ye, Wei Gao, Hong Chen, Ting Song, Daqing Wang, Xiaoyun Mao, Changshan Ren

Published in: International Journal of Colorectal Disease | Issue 1/2011

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.

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Title: Aspirin promotes apoptosis in a murine model of colorectal cancer by mechanisms involving downregulation of IL-6–STAT3 signaling pathway
Authors: Yun Tian
Ying Ye
Wei Gao
Hong Chen
Ting Song
Daqing Wang
Xiaoyun Mao
Changshan Ren
Publication date: 01-01-2011
Publisher: Springer-Verlag
Published in: International Journal of Colorectal Disease / Issue 1/2011
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-010-1060-0

At a glance: The STEP trials

Springer Medicine

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

Abstract

Background and aims

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background and aims

Methods

Results

Conclusions

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