, Volume 12, Issue 8, pp 1465–1478

Expression of anti-apoptotic factors modulates Apo2L/TRAIL resistance in colon carcinoma cells


  • Mara S. Lippa
    • Department of OncologyAmgen Inc.
  • Laura D. Strockbine
    • Department of OncologyAmgen Inc.
  • Tiep T. Le
    • Department of OncologyAmgen Inc.
  • Daniel G. Branstetter
    • Department of PathologyAmgen Inc.
  • Craig A. Strathdee
    • Department of OncologyAmgen Inc.
    • Department of OncologyAmgen Inc.
Original Paper

DOI: 10.1007/s10495-007-0076-6

Cite this article as:
Lippa, M.S., Strockbine, L.D., Le, T.T. et al. Apoptosis (2007) 12: 1465. doi:10.1007/s10495-007-0076-6


Tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) selectively induces apoptosis in transformed cells. Normal cells and certain tumor cells can evade Apo2L/TRAIL induced cell death, but the determinants of Apo2L/TRAIL sensitivity are poorly understood. To better understand the factors that contribute to Apo2L/TRAIL resistance, we characterized two colon carcinoma lines with pronounced differences in Apo2L/TRAIL sensitivity. Colo205 cells are highly sensitive to Apo2L/TRAIL whereas Colo320 cells are unresponsive. Components of the DISC (death inducing signaling complex) could be immunoprecipitated from both cell lines in response to Apo2L/TRAIL. Sensitizing agents including a proteasome inhibitor conferred Apo2L/TRAIL sensitivity in Colo320 cells, indicating that the apoptotic machinery was intact and functional. We specifically suppressed the expression of Bcl-2, FLIP or XIAP in Colo320 cells. Downregulation of either FLIP or XIAP but not Bcl-2 restored sensitivity of Colo320 cells to Apo2L/TRAIL. Moreover, stable knockdown of XIAP expression in Colo320 subcutaneous tumors resulted in suppression of tumor growth and sensitivity to Apo2L/TRAIL in vivo. Our results indicate that only a specific subset of anti-apoptotic proteins can confer resistance to Apo2L/TRAIL in Colo320 cells. Elucidation of the factors that contribute to Apo2L/TRAIL resistance in tumor cells may provide insight into combination therapies with Apo2L/TRAIL in a clinical setting.


Apo2L/TRAIL XIAP shRNA Colorectal cancer Resistance Xenograft

Copyright information

© Springer Science+Business Media, LLC 2007