Velcade sensitizes prostate cancer cells to TRAIL induced apoptosis and suppresses tumor growth in vivo

Perry A. Christian, Jeffery A. Thorpe, Steven R. Schwarze

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Inducing apoptosis via the extrinsic death receptor pathway is an attractive anti-cancer treatment strategy, however, numerous cancer cells exhibit significant resistance to death ligand stimuli. Here, we investigated the anti-neoplastic capability of proteasome inhibition, through the administration of Velcade, to synergize with a death receptor agonist in vivo. The death ligand-resistant LNCaP prostate xenograft model was utilized. Tumors were established and mice were treated with Velcade, TRAIL (TNF-Related Apoptosis Inducing Ligand) or the combined regimen. Only mice treated with a combination of Velcade and TRAIL was tumor growth inhibited with a corresponding loss of the hemorrhagic phenotype, decreased tumor cell proliferation and increased tumor cell apoptosis. Next, to determine if the extrinsic pathway is critical for mediating the anti-tumor efficacy that can be achieved in some cell types with Velcade treatment alone, the death receptor sensitive PC-3 xenograft model was used. PC-3 tumors exhibited a 54% decrease in tumor volume in response to Velcade, while c-FLIP overexpressing PC-3 xenografts were resistant to the treatment. These findings suggest that the extrinsic apoptotic pathway can mediate the anti-tumor effects of Velcade and support the therapeutic use of proteasome inhibition in combination with a death receptor stimulus in the treatment of prostate cancer.

Original languageEnglish
Pages (from-to)73-80
Number of pages8
JournalCancer Biology and Therapy
Issue number1
StatePublished - Jan 2009

Bibliographical note

Funding Information:
The Markey Foundation and Department of Defense Prostate Cancer Program grant (W81XWH-08-1-0392).


  • Apoptosis
  • Prostate cancer
  • Velcade
  • Xenograft

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research


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