Retrovirus-mediated transduction of TRAIL and chemotherapeutic agents co-operatively induce apoptotic cell death in both sarcoma and myeloma cells

Anticancer Res. 2003 Jul-Aug;23(4):3247-53.

Abstract

Background: Resistance to multiple chemotherapeutic agents results from a variety of factors including a lack of apoptosis in tumor cells. To induce apoptosis in two types of tumor cells, RPMI-8226 and MG-63, a combination of chemotherapeutic agents and retroviral transduction of TRAIL was employed.

Materials and methods: Both TRAIL-sensitive 8226 and -resistant MG-63 cells were pretreated with the anti-tumor agent doxorubicin or cisplatin for 24 hours, washed and then exposed to retroviral transduction with TRAIL for a further 24 hours, followed by assay for cell survival using a WST-8 kit.

Results: Doxorubicin or cisplatin sensitized both RPMI-8226 and MG-63 cells to TRAIL-induced death in a synergistic manner. This combined treatment was also effective in the MG-63 cells overexpressing Bcl-xL, which are resistant to multiple chemotherapeutic agents.

Conclusion: A retroviral transduction of TRAIL in conjunction with anti-tumor agents could provide a new treatment modality for the treatment of patients with multiple-drug resistance.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / therapy*
  • Cisplatin / pharmacology*
  • Combined Modality Therapy
  • Doxorubicin / pharmacology*
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Drug Synergism
  • Genetic Therapy
  • Humans
  • Membrane Glycoproteins / genetics*
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / genetics
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / therapy*
  • Osteosarcoma / drug therapy
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / therapy*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Retroviridae / genetics
  • TNF-Related Apoptosis-Inducing Ligand
  • Transduction, Genetic / methods
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / genetics*
  • bcl-X Protein

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • BCL2L1 protein, human
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • bcl-X Protein
  • Doxorubicin
  • Cisplatin