Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model

Yin,Tao; He,Sisi; Shen,Guobo; Ye,Tinghong; Guo,Fuchun; Wang,Yongsheng

doi:10.3892/mmr.2015.3967

Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model

Authors:
- Tao Yin
- Sisi He
- Guobo Shen
- Tinghong Ye
- Fuchun Guo
- Yongsheng Wang
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Affiliations: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: June 22, 2015 https://doi.org/10.3892/mmr.2015.3967
Pages: 4103-4108
Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Neuropsychological factors have been shown to influence tumor progression and therapeutic response. The present study investigated the effect of the dopamine receptor antagonist thioridazine on murine breast cancer. The anti‑tumor efficacy of thioridazine was assessed using a murine breast cancer model. Cell apoptosis and proliferation were analyzed in vitro using flow cytometry (FCM) and the MTT assay, respectively. Western blot analysis was performed to assess Akt, phosphorylated (p)‑Akt, signal transducer and activator of transcription (STAT) 3, p‑STAT3 and p‑p65 in tumor cells following treatment with thioridazine. The Ki67 index and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)‑positive apoptotic cells were assessed in the tumor sections. Thioridazine was found to reduce tumor growth, inhibit tumor cell proliferation and induce apoptosis in a dose‑ and time‑dependent manner in vitro. Thioridazine was also found to markedly inhibit tumor proliferation and induce tumor cell apoptosis in vivo as shown by the lower Ki67 index and increase in TUNEL‑positive cells. In addition, thioridazine was observed to inhibit the activation of the canonical nuclear factor κ‑light‑chain‑enhancer of activated B cells pathway and exert anti‑tumor effects by remodeling the tumor stroma, as well as inhibit angiogenesis in the tumor microenvironment. In conclusion, thioridazine was found to significantly inhibit breast tumor growth and the potential for thioridazine to be used in cancer therapy may be re‑evaluated and investigated in clinical settings.

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