Retrovirus-mediated transduction of TRAIL and chemotherapeutic agents co-operatively induce apoptotic cell death in both sarcoma and myeloma cells |
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Authors: | Suzuki Hidekazu Hotta Takahito Koyama Takashi Komagata Masashi Imakiire Atsuhiro Yanase Noriko Yoshimoto Takayuki Mizuguchi Junichiro |
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Affiliation: | Department of Immunology, Tokyo Medical University, Department of Orthopedic Surgery, Tokyo Medical University Hospital, Tokyo, Japan. |
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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. |
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