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

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.

• Authors: Hidekazu Suzuki, Takahito Hotta, Takashi Koyama, Masashi Komagata, Atsuhiro Imakiire, Noriko Yanase, Takayuki Yoshimoto, Junichiro Mizuguchi
• Journal: Anticancer research (Anticancer Res) 2003 Jul-Aug Vol. 23 Issue 4 Pg. 3247-53 ISSN: 0250-7005 [Print] Greece
• PMID: 12926060 (Publication Type: Journal Article)

Chemical References

• 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

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects, genetics)
• Apoptosis Regulatory Proteins
• Bone Neoplasms (drug therapy, genetics, metabolism, 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, genetics, metabolism, therapy)
• Osteosarcoma (drug therapy, genetics, metabolism, 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