The impact of enzastaurin (LY317615.HCl) on CA125 biosynthesis and shedding in ovarian cancer cells
By: Cadron I, Van Gorp T, Mihalyi A, Luyten C, Drijkoningen K, Amant F, Leunen K, Vergote I.

Division of Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Katholieke Universiteit Leuven, Belgium; Experimental Laboratory of Gynaecologic Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Katholieke Universiteit Leuven, Belgium.
Gynecol Oncol. 2010 May 1.

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 (2-1.000microM), paclitaxel (0.2-100nM) or enzastaurin (1-100microM) 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.

Conclusion

These results suggest that enzastaurin, as paclitaxel, has a direct stimulatory effect on CA 125 synthesis and shedding in vitro. Copyright © 2010 Elsevier Inc. All rights reserved.

PMID: 20439112 [PubMed - as supplied by publisher] Source: National Library of Medicine.






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