The impact of enzastaurin (LY317615.HCl) on CA125 biosynthesis and shedding in ovarian cancer cells.
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.
Cadron
Isabelle
I
Division of Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Katholieke Universiteit Leuven, Belgium. Isabelle.Cadron@uz.kuleuven.ac.be
Van Gorp
Toon
T
Mihalyi
Attila
A
Luyten
Catherina
C
Drijkoningen
Katrien
K
Amant
Frederic
F
Leunen
Karin
K
Vergote
Ignace
I
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
D000970:Antineoplastic Agents; D018394:CA-125 Antigen; D007211:Indoles; D016190:Carboplatin; D017239:Paclitaxel; C504878:enzastaurin