Additive effect of Apo2L/TRAIL and Adeno-p53 in the induction of apoptosis in myeloma cell lines

Exp Hematol. 2001 Aug;29(8):962-70. doi: 10.1016/s0301-472x(01)00677-4.


Objective: We have previously shown that Adenovirus-p53 (Ad-p53) is a potent inducer of apoptosis in myeloma cells expressing nonfunctional p53 and low levels of bcl-2 and that Apo2L/TRAIL is a potent inducer of apoptosis, independent of bcl-2. A study was designed to test the synergy between Ad-p53 and Apo2L/TRAIL in the induction of apoptosis in relation to the expression of DR4/DR5 and DcR1, in cells undergoing Ad-p53-induced apoptosis.

Methods: Replication deficient Ad-p53 and human recombinant Apo2L/TRAIL were used. Myeloma cells with mutated/w.t. p53 and varying expression of bcl-2 were used to test the effect of Ad-p53, Apo2L/TRAIL, or both, on apoptosis, measured by annexin V.

Results: Treatment with Ad-p53 resulted in a dose-dependent apoptosis concomitant with a dose-dependent increase in the expression of DR4/DR5 and a decrease in the expression of DcR1, in Ad-p53-sensitive cell lines. In these cells, addition of Apo2L/TRAIL to cells treated with Ad-p53 resulted in a dose-dependent increase in apoptosis. Myeloma cells resistant to Ad-p53 had high levels of DR4/DR5 and high levels of DcR1 and treatment with Ad-p53 did not reduce the expression of DcR1. Also, addition of Apo2L/TRAIL to Ad-p53 did not affect the level of apoptosis beyond the level of apoptosis observed with Apo2L/TRAIL alone.

Conclusions: 1) Cotreatment with Ad-p53 and Apo2L/TRAIL resulted in additive apoptosis in myeloma cells expressing nonfunctional p53 and low levels of bcl-2. 2) Resistance to Ad-p53 or to the combination of Ad-p53 and Apo2L/TRAIL was not due to the lack of adenovirus receptor (CAR) or low expression of DR4/DR5 but rather due to the relatively high expression of DcR1 receptor.

MeSH terms

  • Adenoviridae
  • Annexin A5 / analysis
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • Genes, bcl-2
  • Genes, p53*
  • HLA-DR4 Antigen / analysis
  • HLA-DR4 Antigen / genetics
  • HLA-DR5 Antigen / analysis
  • HLA-DR5 Antigen / genetics
  • Humans
  • Kinetics
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Multiple Myeloma / pathology*
  • Mutagenesis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Recombinant Proteins / metabolism
  • TNF-Related Apoptosis-Inducing Ligand
  • Transfection / methods
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / physiology*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*


  • Annexin A5
  • Apoptosis Regulatory Proteins
  • HLA-DR4 Antigen
  • HLA-DR5 Antigen
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53