Proteasome inhibition by bortezomib decreases proliferation and increases apoptosis in ovarian granulosa cell tumors

Simon Chu, Maria Alexiadis, Peter J. Fuller

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9 Citations (Scopus)

Abstract

Granulosa cell tumors of the ovary represent ĝ̂1/45% of malignant ovarian tumors. The molecular pathogenesis of granulosa cell tumors is not known but 2 human granulosa cell tumorĝ€"derived cell lines, COV434 and KGN, exhibit constitutive activation of the nuclear factor kappa-B (NFKB)-signaling pathway. The proteasomal inhibitor, bortezomib, has a complex mode of action which includes inhibition of NFKB 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 NFKB 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.

Original languageEnglish
Pages (from-to)397-407
Number of pages11
JournalReproductive Sciences
Volume16
Issue number4
DOIs
Publication statusPublished - Apr 2009
Externally publishedYes

Keywords

  • COV434 cells.
  • KGN cells
  • NFKB
  • Ovarian cancer

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