Perifosine and sorafenib combination induces mitochondrial cell death and antitumor effects in NOD/SCID mice with Hodgkin lymphoma cell line xenografts

S. L. Locatelli, A. Giacomini, A. Guidetti, L. Cleris, R. Mortarini, A. Anichini, A. M. Gianni, C. Carlo-Stella

Research output: Contribution to journalArticlepeer-review

Abstract

The effects of the Akt inhibitor perifosine and the RAF/MEK/ERK inhibitor sorafenib were investigated using two CD30+ Hodgkin lymphoma cell lines (L-540 and HDLM-2) and the CD30 - HD-MyZ histiocytic cell line. The combined perifosine/sorafenib treatment significantly inhibited mitogen-activated protein kinase and Akt phosphorylation in two of the three cell lines. Profiling of the responsive cell lines revealed that perifosine/sorafenib decreased the amplitude of transcriptional signatures that are associated with the cell cycle, DNA replication and cell death. Tribbles homolog 3 (TRIB3) was identified as the main mediator of the in vitro and in vivo antitumor activity of perifosine/sorafenib. Combined treatment compared with single agents significantly suppressed cell growth (40-80%, P

Original languageEnglish
Pages (from-to)1677-1687
Number of pages11
JournalLeukemia
Volume27
Issue number8
DOIs
Publication statusPublished - Aug 2013

Keywords

  • Akt inhibitors
  • Hodgkin lymphoma
  • necroptosis
  • perifosine
  • sorafenib
  • tumor xenografts

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

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