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Paroxetine combined with fluorouracil plays a therapeutic role in mouse models of colorectal cancer with depression through inhibiting IL‑22 expression to regulate the MAPK signaling pathway

  • Authors:
    • Huijie Zhang
    • Meixv Chen
    • Ying Liu
    • Xiaomei Dong
    • Chan Zhang
    • Han Jiang
    • Xue Chen

  • View Affiliations

  • Published online on: October 22, 2020     https://doi.org/10.3892/etm.2020.9370
  • Article Number: 240

  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The objective of the present study was to observe the therapeutic effect of paroxetine combined with fluorouracil on mice with colorectal cancer (CRC) complicated with depression and to explore its mechanism of action. Using chronic mild stress and xenograft tumor methods to model CRC complicated with depression, 60 BALB/c mice were randomly divided into control, tumor model, tumor depression model, tumor depression antidepressant, tumor depression chemotherapy and tumor depression antidepressant plus chemotherapeutic drug groups. Changes in mouse sucrose preference and forced swimming tests were tracked. Changes in tumor volume and weight were compared, the tumor inhibition rate was calculated, Ki‑67 expression in tumor tissues was detected using immunohistochemistry and IL‑22 levels in peripheral blood were detected using ELISAs. Additionally, protein expression levels of IL‑22, Bcl‑2, Bax, caspase‑3, p38, phosphorylated (p)‑p38, ERK, p‑ERK, JNK and p‑JNK in tumor tissue were detected using western blotting. Following treatment with paroxetine and chemotherapy drugs, the sucrose preference index was increased, autonomic behavior dysfunction was alleviated and tumor growth was significantly inhibited. Furthermore, the expression levels of Ki‑67 and apoptosis‑related proteins, Bax and caspase‑3, increased in tumor tissues, anti‑apoptosis protein Bcl2 expression levels decreased significantly, IL‑22 levels in the blood and tumor tissues were reduced and p‑p38, p‑ERK and p‑JNK proteins were significantly reduced. It was concluded that paroxetine combined with chemotherapy drugs improved depressive behavior and promoted the survival state in a mouse model of CRC and depression, possibly through inhibiting IL‑22 expression to regulate the activity of the MAPK signaling pathway.
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December-2020
Volume 20 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhang H, Chen M, Liu Y, Dong X, Zhang C, Jiang H and Chen X: Paroxetine combined with fluorouracil plays a therapeutic role in mouse models of colorectal cancer with depression through inhibiting IL‑22 expression to regulate the MAPK signaling pathway. Exp Ther Med 20: 240, 2020
APA
Zhang, H., Chen, M., Liu, Y., Dong, X., Zhang, C., Jiang, H., & Chen, X. (2020). Paroxetine combined with fluorouracil plays a therapeutic role in mouse models of colorectal cancer with depression through inhibiting IL‑22 expression to regulate the MAPK signaling pathway. Experimental and Therapeutic Medicine, 20, 240. https://doi.org/10.3892/etm.2020.9370
MLA
Zhang, H., Chen, M., Liu, Y., Dong, X., Zhang, C., Jiang, H., Chen, X."Paroxetine combined with fluorouracil plays a therapeutic role in mouse models of colorectal cancer with depression through inhibiting IL‑22 expression to regulate the MAPK signaling pathway". Experimental and Therapeutic Medicine 20.6 (2020): 240.
Chicago
Zhang, H., Chen, M., Liu, Y., Dong, X., Zhang, C., Jiang, H., Chen, X."Paroxetine combined with fluorouracil plays a therapeutic role in mouse models of colorectal cancer with depression through inhibiting IL‑22 expression to regulate the MAPK signaling pathway". Experimental and Therapeutic Medicine 20, no. 6 (2020): 240. https://doi.org/10.3892/etm.2020.9370