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Reproductive Sciences
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Article

Proteasome Inhibition by Bortezomib Decreases Proliferation and Increases Apoptosis in Ovarian Granulosa Cell Tumors

Simon Chu, Maria Alexiadis, and Peter James Fuller*

* To whom correspondence should be addressed. E-mail: peter.fuller{at}princehenrys.org.


  Abstract

Granulosa cell tumors of the ovary represent ~5% of malignant ovarian tumors. The molecular pathogenesis of granulosa cell tumors is not known but 2 human granulosa cell tumor–derived cell lines, COV434 and KGN, exhibit constitutive activation of the nuclear factor kappa-B (NF{kappa}B)-signaling pathway. The proteasomal inhibitor, bortezomib, has a complex mode of action which includes inhibition of NF{kappa}B signaling. We examined the effect of bortezomib on the COV434 and KGN cells. The COV434 and KGN cells both showed a dose-dependent inhibition of cell proliferation and viability in response to bortezomib together with an increase in apoptosis. This was achieved at concentrations within the range seen for clinically responsive tumors. The NF{kappa}B constitutive activity was not however decreased. Genes were identified that were regulated in both lines in response to bortezomib. This study suggests that advanced granulosa cell tumors, as represented by the cell lines, may respond to bortezomib either alone or in combination with other agents.

First published on December 15, 2008, doi:10.1177/1933719108327589

Reproductive Sciences 2009;16:397.

A more recent version of this article appeared on April 1, 2009

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