DR2 blocker thioridazine: A promising drug for ovarian cancer therapy

  • Authors:
    • Min Yong
    • Tinghe Yu
    • Si Tian
    • Shuaibin Liu
    • Jiao Xu
    • Jianguo Hu
    • Lina Hu
  • View Affiliations

  • Published online on: October 16, 2017     https://doi.org/10.3892/ol.2017.7184
  • Pages:8171-8177
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Abstract

Dopamine receptor 2 (DR2) may be a biomarker for various types of cancer. Ovarian cancer cells overexpress DR2; therefore, blocking DR2 may be a novel treatment strategy for ovarian cancer. Thioridazine, a DR2 blocker, has antineoplastic activity in a variety of cancer cells. In view of the requirement for novel therapeutic agents in ovarian cancer, the present study aimed to determine the potential effects of thioridazine in vitro and in vivo. It was revealed that the DR2 blocker thioridazine induced cell death in a dose‑dependent manner in ovarian cancer cells. Thioridazine treatment induced apoptosis and autophagy, which may be attributed to an increased level of reactive oxygen species and associated DNA damage. Additionally, the expression of various proteins increased with oxidative stress, including nuclear factor E2‑related factor 2, which is a pivotal transcriptional factor involved in cellular responses to oxidative stress. Heme oxygenase 1, NAPDH quinone dehydrogenase 1 and hypoxia inducible factor‑1α and phosphorylated (p)‑protein kinase B expression was significantly decreased, and the expression level of p‑extracellular signal‑related kinases and p‑P38 was increased. Using 3‑methyl adenine to inhibit autophagy caused the rate of apoptosis to increase. Thioridazine inhibited the growth of SKOV3 xenografts in nude mice. The present study demonstrated that the DR2 blocker thioridazine exhibited anticancer effects in vitro and in vivo, suggesting that thioridazine may be used as a potential drug in ovarian cancer therapy.

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December 2017
Volume 14 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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Copy and paste a formatted citation
APA
Yong, M., Yu, T., Tian, S., Liu, S., Xu, J., Hu, J., & Hu, L. (2017). DR2 blocker thioridazine: A promising drug for ovarian cancer therapy. Oncology Letters, 14, 8171-8177. https://doi.org/10.3892/ol.2017.7184
MLA
Yong, M., Yu, T., Tian, S., Liu, S., Xu, J., Hu, J., Hu, L."DR2 blocker thioridazine: A promising drug for ovarian cancer therapy". Oncology Letters 14.6 (2017): 8171-8177.
Chicago
Yong, M., Yu, T., Tian, S., Liu, S., Xu, J., Hu, J., Hu, L."DR2 blocker thioridazine: A promising drug for ovarian cancer therapy". Oncology Letters 14, no. 6 (2017): 8171-8177. https://doi.org/10.3892/ol.2017.7184