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Article

Activation of the mTORC1 and STAT3 pathways promotes the malignant transformation of colitis in mice

  • Authors:
    • Zhen He
    • Xiaosheng He
    • Zexian Chen
    • Jia Ke
    • Xiaowen He
    • Ruixue Yuan
    • Zerong Cai
    • Xiuting Chen
    • Xiaojian Wu
    • Ping Lan
  • View Affiliations / Copyright

    Affiliations: Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China, Gastrointestinal Institute, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
  • Pages: 1873-1880
    |
    Published online on: August 20, 2014
       https://doi.org/10.3892/or.2014.3421
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Abstract

Chronic inflammation is an underlying risk factor for colorectal cancer. No direct evidence has proven that inflammation in the colon promotes carcinogenesis. STAT3 plays an important role in the development of colitis-associated colorectal cancer (CAC). There is crosstalk between the mammalian target of rapamycin complex 1 (mTORC1) and the STAT3 pathways. The aim of the present study was to confirm that colitis promotes CAC and if so, to explore the function of the STAT3 and mTORC1 pathways in CAC. C57BL/6 mice were treated with axozymethane (AOM) and dextran sulfate sodium (DSS) to induce CAC. By varying the concentration of DSS (0, 1 and 2% respectively), we mimicked the CAC model with different degrees of inflammation and determined the risk of carcinogenesis. Expression of the STAT3 and mTORC1 pathways was detected. Finally, rapamycin, an mTORC1 inhibitor, was used to treat the CAC model. Tumor load, protein and gene expression of chemokines were determined. The multiplicity and tumor load of the high inflammation group were higher than those of the low inflammation group. Immunohistochemical staining and western blot analysis revealed that activation of the STAT3 and mTORC1 pathways increased gradually in the inflammation tissues and tumors. When we treated the mice with rapamycin, the tumor incidence, multiplicity and tumor load decreased. In addition, rapamycin widely suppressed the expression of pro‑inflammatory and anti-inflammatory chemokines in the tissues, including tumor necrosis factor-α, interferon-γ, IL-6, IL-10 and IL-12α. In conclusion, inflammation promotes the development of CAC via the STAT3 and mTORC1 pathways, which may be a viable treatment strategy for the chemoprevention of CAC.
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Copy and paste a formatted citation
Spandidos Publications style
He Z, He X, Chen Z, Ke J, He X, Yuan R, Cai Z, Chen X, Wu X, Lan P, Lan P, et al: Activation of the mTORC1 and STAT3 pathways promotes the malignant transformation of colitis in mice. Oncol Rep 32: 1873-1880, 2014.
APA
He, Z., He, X., Chen, Z., Ke, J., He, X., Yuan, R. ... Lan, P. (2014). Activation of the mTORC1 and STAT3 pathways promotes the malignant transformation of colitis in mice. Oncology Reports, 32, 1873-1880. https://doi.org/10.3892/or.2014.3421
MLA
He, Z., He, X., Chen, Z., Ke, J., He, X., Yuan, R., Cai, Z., Chen, X., Wu, X., Lan, P."Activation of the mTORC1 and STAT3 pathways promotes the malignant transformation of colitis in mice". Oncology Reports 32.5 (2014): 1873-1880.
Chicago
He, Z., He, X., Chen, Z., Ke, J., He, X., Yuan, R., Cai, Z., Chen, X., Wu, X., Lan, P."Activation of the mTORC1 and STAT3 pathways promotes the malignant transformation of colitis in mice". Oncology Reports 32, no. 5 (2014): 1873-1880. https://doi.org/10.3892/or.2014.3421
Copy and paste a formatted citation
x
Spandidos Publications style
He Z, He X, Chen Z, Ke J, He X, Yuan R, Cai Z, Chen X, Wu X, Lan P, Lan P, et al: Activation of the mTORC1 and STAT3 pathways promotes the malignant transformation of colitis in mice. Oncol Rep 32: 1873-1880, 2014.
APA
He, Z., He, X., Chen, Z., Ke, J., He, X., Yuan, R. ... Lan, P. (2014). Activation of the mTORC1 and STAT3 pathways promotes the malignant transformation of colitis in mice. Oncology Reports, 32, 1873-1880. https://doi.org/10.3892/or.2014.3421
MLA
He, Z., He, X., Chen, Z., Ke, J., He, X., Yuan, R., Cai, Z., Chen, X., Wu, X., Lan, P."Activation of the mTORC1 and STAT3 pathways promotes the malignant transformation of colitis in mice". Oncology Reports 32.5 (2014): 1873-1880.
Chicago
He, Z., He, X., Chen, Z., Ke, J., He, X., Yuan, R., Cai, Z., Chen, X., Wu, X., Lan, P."Activation of the mTORC1 and STAT3 pathways promotes the malignant transformation of colitis in mice". Oncology Reports 32, no. 5 (2014): 1873-1880. https://doi.org/10.3892/or.2014.3421
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