title: The impact of enzastaurin (LY317615.HCl) on CA125 biosynthesis and shedding in ovarian cancer cells.
abstract: BACKGROUND
  In this study the modulatory effect of the proteinase kinase C beta (PKC beta) selective inhibitor enzastaurin on CA125 expression and shedding in ovarian cancer cells (OVCAR-3 cells) was investigated. MATERIAL ANDMETHODS: OVCAR-3 cells were cultured in vitro and treated with increasing concentrations of carboplatin (2-1000 microM), paclitaxel (0.2-100 nM) or enzastaurin (1-100 microM) single agent. Growth inhibitory effects were evaluated by MTS and luminescence assay. CA 125 was determined in supernatans and in cell lysate using an electrochemo-iluminescence immunoassay.
  
  
  RESULTS
  Cell growth of OVCAR-3 cells was inhibited by single agent carboplatin, paclitaxel or enzastaurin in a dose dependent manner. Carboplatin caused a transient increase of CA125 in supernatans followed by a gradual decrease of CA125. Treatment with increasing doses of paclitaxel or enzastaurin caused an increase of CA125 shedding in culture medium but also the membrane bound fraction of CA125 was increased.
  
  
  CONCLUSIONS
  These results suggest that enzastaurin, as paclitaxel, has a direct stimulatory effect on CA 125 synthesis and shedding in vitro.
authors.affiliation: Division of Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Katholieke Universiteit Leuven, Belgium. Isabelle.Cadron@uz.kuleuven.ac.be
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cadron
authors.forename: Toon
authors.initials: T
authors.lastname: Van Gorp
authors.forename: Attila
authors.initials: A
authors.lastname: Mihalyi
authors.forename: Catherina
authors.initials: C
authors.lastname: Luyten
authors.forename: Katrien
authors.initials: K
authors.lastname: Drijkoningen
authors.forename: Frederic
authors.initials: F
authors.lastname: Amant
authors.forename: Karin
authors.initials: K
authors.lastname: Leunen
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018394:CA-125 Antigen / Q000096:biosynthesis*; D016190:Carboplatin / Q000494:pharmacology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D018394:CA-125 Antigen; D007211:Indoles; D016190:Carboplatin; D017239:Paclitaxel; C504878:enzastaurin