title: The important application of thioridazine in the endometrial cancer.
abstract: BACKGROUND
  Endometrial cancer (ECa) is one of the serious healthy burden for female worldwide. The treatments of ECa focus on the application of endocrine therapy and aberrant signaling proteins expression recently years. Medroxyprogesterone acrtate (MPA) plays crucial role in the endocrine therapy for ECa patients. However, the outcomes are still not ideal in the advanced stage tumor, especially in the progesterone-resistant ECa. Thioridazine (THIO) is an anti-psychotic agent, which has been reported to suppress the development of several human cancers. In this study, we aimed at to explore the clinical significant of THIO in the treatment of ECa.
  
  
  METHODS
  Two ECa cell lines (ISK and KLE) were enrolled in this study, and were grouped into fore groups based on the treatment with different agents. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was used to analyze the viability of ECa cell lines. The apoptosis of ECa cells was examined by using the flow cytometer. To investigate the expression of important proteins, we applied the quantitative real-time RT-PCR (qRT-PCR) method and western blot analysis.
  
  
  RESULTS
  The viability of ECa cells was downregulated, and the apoptosis of ECa cells was upregulated after treating with the THIO plus MPA. The expression of progesterone receptor B (PRB) and dopamine receptor D2 (DRD2) were increased, and epidermal growth factor receptor (EGFR) and p-AKT were decreased in the THIO+MPA group. All these results suggested that the THIO could promote MPA to inhibit the growth of cells in ECa, especially in the progesterone-resistant ECa.
  
  
  CONCLUSIONS
  Taken together, all the data in the present study suggested that the THIO plus MPA might act as the suppressor of tumor growth in ECa by inhibiting the PI3K/AKT signal transduction pathway, which was mediated by PRB, DRD2 and EGFR.
authors.affiliation: Department of Anesthesiology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Laboratory for Gynecologic Oncology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
keywords: MPA; Thioridazine; endometrial cancer