title: Anti-Proliferative and Apoptotic Activities of Müllerian Inhibiting Substance Combined with Calcitriol in Ovarian Cancer Cell Lines.
abstract: OBJECTIVE
  This study aimed to investigate whether Müllerian inhibiting substance (MIS) in combination with calcitriol modulates proliferation and apoptosis of human ovarian cancer (OCa) cell lines (SKOV3, OVCAR3, and OVCA433) and identify the signaling pathway by which MIS mediates apoptosis.
  
  
  METHODS
  OCa cell lines were treated with MIS in the absence or presence of calcitriol. Cell viability and proliferation were evaluated using the Cell Counting Kit-8 assay and apoptosis was evaluated by DNA fragmentation assay. Western blot and enzyme-linked immunosorbent assay were used to determine the signaling pathway.
  
  
  RESULTS
  The cells showed specific staining for the MIS type II receptor. Treatment of OCa cells with MIS and calcitriol led to dose- and time-dependent inhibition of cell growth and survival. The combination treatment significantly suppressed cell growth, down-regulated the expression of B-cell lymphoma 2 (Bcl-2), and up-regulated the expressions of Bcl-2 associated X protein, caspase-3, and caspase-9 through the extracellular signal-regulated kinase signaling pathway.
  
  
  CONCLUSIONS
  These results, coupled with a much-needed decrease in the toxic side effects of currently employed therapeutic agents, provide a strong rationale for testing the therapeutic potential of MIS, alone or in combination with calcitriol, in the treatment of OCa.
authors.affiliation: Department of Obstetrics and Gynecology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.|Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yeon Soo
authors.initials: YS
authors.lastname: Jung
authors.affiliation: Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.|Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seok Kyo
authors.initials: SK
authors.lastname: Seo
authors.affiliation: Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.|Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Young Sik
authors.initials: YS
authors.lastname: Choi
authors.affiliation: Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.|Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Nam
authors.affiliation: Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.|Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.|Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sang Wun
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Hyuck Dong
authors.initials: HD
authors.lastname: Han
authors.affiliation: Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.|Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jae Wook
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.|Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. ytkchoi@yuhs.ac.
authors.forename: Young Tae
authors.initials: YT
authors.lastname: Kim
mesh_terms: D054304:Anti-Mullerian Hormone / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002117:Calcitriol / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D006131:Growth Inhibitors; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; C084621:anti-Mullerian hormone receptor; D054304:Anti-Mullerian Hormone; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D053453:Caspase 9; D002117:Calcitriol
keywords: Müllerian inhibiting substance; Ovarian cancer; antiproliferation; apoptosis; calcitriol