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


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.


CONCLUSIONS
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.
Suzuki
Hidekazu
H
Department of Immunology, Tokyo Medical University, Department of Orthopedic Surgery, Tokyo Medical University Hospital, Tokyo, Japan.
Hotta
Takahito
T
Koyama
Takashi
T
Komagata
Masashi
M
Imakiire
Atsuhiro
A
Yanase
Noriko
N
Yoshimoto
Takayuki
T
Mizuguchi
Junichiro
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D015316:Genetic Therapy; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012190:Retroviridae / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand; D014161:Transduction, Genetic / Q000379:methods; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D051020:bcl-X Protein
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D004317:Doxorubicin; D002945:Cisplatin