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

Simon Chu, PhD

Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia

Maria Alexiadis, BSc Hons

Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia

Peter J. Fuller, PhD, FRACP

Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia, peter.fuller{at}princehenrys.org

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.

Key Words: Ovarian cancer • NF{kappa}B • KGN cells • COV434 cells.

This version was published on April 1, 2009

Reproductive Sciences, Vol. 16, No. 4, 397-407 (2009)
DOI: 10.1177/1933719108327589
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