TY - JOUR AB - 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. AD - Department of Psychiatry, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China AU - Zhang,Huijie AU - Chen,Meixv AU - Liu,Ying AU - Dong,Xiaomei AU - Zhang,Chan AU - Jiang,Han AU - Chen,Xue DA - 2020/12/01 DO - 10.3892/etm.2020.9370 IS - 6 JO - Exp Ther Med KW - colorectal cancer depression paroxetine mitogen‑ associated protein kinase signaling pathway PY - 2020 SN - 1792-0981 1792-1015 SP - 240 ST - 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 T2 - Experimental and Therapeutic Medicine TI - 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 UR - https://doi.org/10.3892/etm.2020.9370 VL - 20 ER -