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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
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
    Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 4103-4108
    |
    Published online on: June 22, 2015
       https://doi.org/10.3892/mmr.2015.3967
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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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1 

Schuller HM, Al-Wadei H, Ullah MF and Plummer HK III: Regulation of pancreatic cancer by neuropsychological stress responses: a novel target for intervention. Carcinogenesis. 33:191–196. 2012. View Article : Google Scholar :

2 

Thaker PH, Han LY, Kamat AA, et al: Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med. 12:939–944. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Melhem-Bertrandt A, Chavez-MacGregor M, Lei X, et al: Beta-blocker use is associated with improved relapse-free survival in patients with triple-negative breast cancer. J Clin Oncol. 29:2645–2652. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Lemeshow S, Sørensen HT, Phillips G, et al: β-blockers and survival among Danish patients with malignant melanoma: a population-based cohort study. Cancer Epidemiol Biomarkers Prev. 20:2273–2279. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Grytli HH, Fagerland MW, Fosså SD, et al: Use of β-blockers is associated with prostate cancer-specific survival in prostate cancer patients on androgen deprivation therapy. Prostate. 73:250–260. 2013. View Article : Google Scholar

6 

Magnon C, Hall SJ, Lin J, et al: Autonomic nerve development contributes to prostate cancer progression. Science. 341:12363612013. View Article : Google Scholar : PubMed/NCBI

7 

Sarkar DK, Zhang C, Murugan S, et al: Transplantation of β-endorphin neurons into the hypothalamus promotes immune function and restricts the growth and metastasis of mammary carcinoma. Cancer Res. 71:6282–6291. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Yamazaki S, Ema H, Karlsson G, et al: Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche. Cell. 147:1146–1158. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Lucas D, Scheiermann C, Chow A, et al: Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration. Nat Med. 19:695–703. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Sibley DR and Monsma FJ Jr: Molecular biology of dopamine receptors. Trends Pharmacol Sci. 13:61–69. 1992. View Article : Google Scholar : PubMed/NCBI

11 

González H, Contreras F, Prado C, et al: Dopamine receptor D3 expressed on CD4+ T cells favors neurodegeneration of dopaminergic neurons during Parkinson's Disease. J Immunol. 190:5048–5056. 2013. View Article : Google Scholar

12 

Pacheco R, Prado CE, Barrientos MJ and Bernales S: Role of dopamine in the physiology of T-cells and dendritic cells. J Neuroimmunol. 216:8–19. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Saha B, Mondal AC, Basu S and Dasgupta PS: Circulating dopamine level, in lung carcinoma patients, inhibits proliferation and cytotoxicity of CD4+ and CD8+ T cells by D1 dopamine receptors: an in vitro analysis. Int Immunopharmacol. 1:1363–1374. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Sachlos E, Risueño RM, Laronde S, et al: Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells. Cell. 149:1284–1297. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Seeman P and Lee T: Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science. 188:1217–1219. 1975. View Article : Google Scholar : PubMed/NCBI

16 

Ly KL, Chidgey J, Addington-Hall J and Hotopf M: Depression in palliative care: a systematic review. Part 2. Treatment. Palliat Med. 16:279–284. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Zhukovsky DS: Fever and sweats in the patient with advanced cancer. Hematol Oncol Clin North Am. 16:579–588. 2002. View Article : Google Scholar : PubMed/NCBI

18 

Rho SB, Kim BR and Kang S: A gene signature-based approach identifies thioridazine as an inhibitor of phosphatidylinositol-3′-kinase (PI3K)/AKT pathway in ovarian cancer cells. Gynecol Oncol. 120:121–127. 2011. View Article : Google Scholar

19 

Engelman JA: Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 9:550–562. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Osaki M, Oshimura M and Ito H: PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis. 9:667–676. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Corvinus FM, Orth C, Moriggl R, et al: Persistent STAT3 activation in colon growth. Neoplasia. 7:545–555. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Sherry MM, Reeves A, Wu JK and Cochran BH: STAT3 is required for proliferation and maintenance of multipotency in glioblastoma stem cells. Stem Cells. 27:2383–2392. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Bassères DS and Baldwin AS: Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression. Oncogene. 25:6817–6830. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Lam LT, Davis RE, Pierce J, et al: Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups of diffuse large B-cell lymphoma defined by gene expression profiling. Clin Cancer Res. 11:28–40. 2005.PubMed/NCBI

25 

Weis SM and Cheresh DA: Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med. 17:1359–1370. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Byun HJ, Lee JH, Kim BR, et al: Anti-angiogenic effects of thioridazine involving the FAK-mTOR pathway. Microvasc Res. 84:227–234. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Lechertier T and Hodivala-Dilke K: Focal adhesion kinase and tumour angiogenesis. J Pathol. 226:404–412. 2012. View Article : Google Scholar

28 

Ponti D, Costa A, Zaffaroni N, et al: Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 65:5506–5511. 2005. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yin T, He S, Shen G, Ye T, Guo F and Wang Y: Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model. Mol Med Rep 12: 4103-4108, 2015.
APA
Yin, T., He, S., Shen, G., Ye, T., Guo, F., & Wang, Y. (2015). Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model. Molecular Medicine Reports, 12, 4103-4108. https://doi.org/10.3892/mmr.2015.3967
MLA
Yin, T., He, S., Shen, G., Ye, T., Guo, F., Wang, Y."Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model". Molecular Medicine Reports 12.3 (2015): 4103-4108.
Chicago
Yin, T., He, S., Shen, G., Ye, T., Guo, F., Wang, Y."Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model". Molecular Medicine Reports 12, no. 3 (2015): 4103-4108. https://doi.org/10.3892/mmr.2015.3967
Copy and paste a formatted citation
x
Spandidos Publications style
Yin T, He S, Shen G, Ye T, Guo F and Wang Y: Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model. Mol Med Rep 12: 4103-4108, 2015.
APA
Yin, T., He, S., Shen, G., Ye, T., Guo, F., & Wang, Y. (2015). Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model. Molecular Medicine Reports, 12, 4103-4108. https://doi.org/10.3892/mmr.2015.3967
MLA
Yin, T., He, S., Shen, G., Ye, T., Guo, F., Wang, Y."Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model". Molecular Medicine Reports 12.3 (2015): 4103-4108.
Chicago
Yin, T., He, S., Shen, G., Ye, T., Guo, F., Wang, Y."Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model". Molecular Medicine Reports 12, no. 3 (2015): 4103-4108. https://doi.org/10.3892/mmr.2015.3967
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