title: Estrogen combined with progesterone decreases cell proliferation and inhibits the expression of Bcl-2 via microRNA let-7a and miR-34b in ovarian cancer cells.
abstract: OBJECTIVE
  This study evaluated the effect of estrogen (E(2)), progesterone (P4), and the combination of them (E(2) + P4) on survival rate, apoptosis, and the expressions of Bcl-2, hsa-let-7a and has-miR-34b in primary ovarian cancer cells to provide new clues for the clinical treatments of ovarian cancer.
  
  
  METHODS
  The primary ovarian cancer cells from 60 cases of clinical ovarian cancer tissues were isolated and then cultured. The survival rate of ovarian cancer cells after the treatment of E(2), P4 and E(2) + P4 was analyzed by MTT assay. Cell apoptosis rate and cell cycle were measured by FACS analysis. Moreover, the relative abundance of Bcl-2 and microRNAs (let-7a, miR-34b) expressions were detected by quantitative real-time PCR (qRT-PCR) and Western blotting.
  
  
  RESULTS
  Low concentrations of estrogen (10(-10), 10(-8), 10(-6 )mol/L) did not affect the proliferation of ovarian cancer cells. However, the high concentration of estrogen (10(-4 )mol/L) inhibited survival rate of ovarian cancer cells. Progesterone (10(-4 )mol/L) inhibited the proliferation of cancer cells. The combination of estrogen and progesterone significantly inhibited the survival rate of ovarian cancer cells with a time- and dose-dependent manner. High concentration of estrogen combined with progesterone (E(2) + P4) induced apoptosis of ovarian cancer cells. E(2) + P4 promoted the expression of let-7a and miR-34b and reduced the expression of Bcl-2 in ovarian cancer cells. When the expression of let-7a or/and miR-34b was inhibited using miRNA inhibitors, E(2) + P4 treatment did not change the protein level of Bcl-2.
  
  
  CONCLUSIONS
  E(2) + P4 significantly inhibited the cell survival, promoted the cell apoptosis, induced the expression of let-7a and miR-34b, and reduced the expression of Bcl-2 in ovarian cancer cells.
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Zhong Shan Road 321#, Nanjing, 210008, China, xieyulianxy@126.com.
authors.forename: Y L
authors.initials: YL
authors.lastname: Xie
authors.forename: Y J
authors.initials: YJ
authors.lastname: Yang
authors.forename: C
authors.initials: C
authors.lastname: Tang
authors.forename: H J
authors.initials: HJ
authors.lastname: Sheng
authors.forename: Y
authors.initials: Y
authors.lastname: Jiang
authors.forename: K
authors.initials: K
authors.lastname: Han
authors.forename: L J
authors.initials: LJ
authors.lastname: Ding
mesh_terms: D018262:Adenocarcinoma, Clear Cell; D002288:Adenocarcinoma, Mucinous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000187:drug effects / Q000235:genetics; D008875:Middle Aged; D018297:Neoplasms, Cystic, Mucinous, and Serous; D010051:Ovarian Neoplasms; D011374:Progesterone / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics; D013724:Teratoma; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: C000595707:BCL2 protein, human; D004967:Estrogens; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; C487931:mirnlet7 microRNA, human; D011374:Progesterone