Primary ovarian cancer cells are sensitive to the proaptotic effects of proteasome inhibitors

Luca Pasquini, Alessia Petronelli, Eleonora Petrucci, Ernestina Saulle, Gualtiero Mariani, Giovanni Scambia, Pierluigi Benedetti-Panici, Stefano Greggi, Francesco Cognetti, Ugo Testa

Research output: Contribution to journalArticle

Abstract

Resistance of tumors to cell death signals poses a complex clinical problem. In the present study, we have explored the capacity of proteasome inhibitors to induce cell death of ovarian cancer cells. We explored the sensitivity of primary ovarian cancer cells to a combination of bortezomib (also known as PS-341), a proteasome inhibitor and TRAIL, a death ligand, or mapatumumab or lexatumumab, TRAIL-R1 or TRAIL-R2 targeting agonist monoclonal antibodies, respectively. The results of our study showed that the large majority of primary ovarian cancers are clearly sensitive to the pro-apoptotic action of bortezomib, whose effects are potentiated by the concomitant addition of TRAIL or mapatumumab or lexatumumab. Interestingly, both cisplatin and paclitaxel-chemosensitive and chemoresistant ovarian tumors are equally sensitive to the cytotoxic effect of bortezomib. Bortezomib, combined with TRAIL or TRAIL-R1 or TRAIL-R2 agonist monoclonal antibodies may be a useful treatment for refractory ovarian cancer.

Original languageEnglish
Pages (from-to)707-713
Number of pages7
JournalInternational Journal of Oncology
Volume36
Issue number3
DOIs
Publication statusPublished - 2010

Keywords

  • Ovarian cancer
  • Proteasome inhibitors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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    Pasquini, L., Petronelli, A., Petrucci, E., Saulle, E., Mariani, G., Scambia, G., Benedetti-Panici, P., Greggi, S., Cognetti, F., & Testa, U. (2010). Primary ovarian cancer cells are sensitive to the proaptotic effects of proteasome inhibitors. International Journal of Oncology, 36(3), 707-713. https://doi.org/10.3892/ijo-00000546