title: [Mechanism of thioridazine plus medroxyprogesterone in the treatment of endometrial cancer].
abstract: OBJECTIVE
  To explore the in vitro effects of thioridazine (THIO) plus medroxyprogesterone (MPA) on the proliferation and apoptosis of endometrial cancer cell lines (Ishikawa & KLE) and examine the mechanism in the treatment of endometrial cancer.
  
  
  METHODS
  CCK-8 assay was employed for detecting the influence of THIO plus MPA on the proliferation and apoptosis of endometrial cancer cells (ISK & KLE). And the concentration and timepoints of drugs were determined according to the results. Real-time polymerase chain reaction (PCR) and Western blot were used to detect the expression levels of PRB, DRD2 and p-AKT/AKT in PI3K/AKT signal pathway. Flow cytometry was applied for detecting the apoptosis of combination (THIO+MPA) and MPA groups.
  
  
  RESULTS
  Compared to MPA group, the proliferation inhibiting effect of combination group increased significantly in ISK and KLE cells (52.5% ± 2.6% vs 37.3% ± 0.3%, P < 0.05; 97.7% ± 0.7% vs 50.0% ± 0.4%, P < 0.001); the apoptotic rates increased (34.0% ± 1.4% vs 50.5% ± 2.4%, P < 0.01; 5.5% ± 3.6% vs 11.3% ± 0.7%, P < 0.01); the expression levels of PRB and DRD2 were up-regulated (all P < 0.05). And the ratio of p-AKT/AKT decreased obviously.
  
  
  CONCLUSIONS
  Thioridazine significantly enhances the effects of MPA on proliferative inhibition and apoptotic promotion in endometrial cancer cells. And it may be associated with the PRB/DRD2-mediated PI3K/AKT signal pathway.
authors.affiliation: International Peace Maternity & Child Health Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Meng
authors.affiliation: International Peace Maternity & Child Health Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.affiliation: International Peace Maternity & Child Health Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: International Peace Maternity & Child Health Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China; Email: owangyudong@126.com.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D016889:Endometrial Neoplasms; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008525:Medroxyprogesterone; D019869:Phosphatidylinositol 3-Kinases; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013881:Thioridazine
chemical_list: D051017:Apoptosis Regulatory Proteins; D019869:Phosphatidylinositol 3-Kinases; D008525:Medroxyprogesterone; D013881:Thioridazine