Ito A, Shinkai M, Honda H, Kobayashi T
Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya 464-8603, Japan.
Cancer Gene Ther. 2001 Sep;8(9):649-54. doi: 10.1038/sj.cgt.7700357.
Heat-induced therapeutic gene expression is highly desired for gene therapy to minimize side effects. Furthermore, if the gene expression is triggered by heat stress, combined therapeutic effects of hyperthermia and gene therapy may be possible. We combined TNF-alpha gene therapy driven by the stress-inducible promoter, gadd 153, with hyperthermia using magnetite cationic liposomes (MCLs). In nude mice, MCLs induced cell death throughout much of the tumor area on heating under an alternating magnetic field. This heat stress also resulted in a 3-fold increase in TNF-alpha gene expression driven by the gadd 153 promoter as compared with that of nonheated tumor. TNF-alpha gene expression was also observed in the peripheral area where the hyperthermic effect was not enough to cause cell death. The combined treatment strongly arrested tumor growth in nude mice over a 30-day period, suggesting potential for cancer treatment.
为了将基因治疗的副作用降至最低，热诱导治疗性基因表达备受期待。此外，如果基因表达由热应激触发，那么热疗和基因治疗的联合治疗效果将成为可能。我们将由应激诱导型启动子gadd 153驱动的肿瘤坏死因子-α（TNF-α）基因治疗与使用磁铁矿阳离子脂质体（MCLs）的热疗相结合。在裸鼠中，MCLs在交变磁场下加热时可诱导肿瘤大部分区域的细胞死亡。与未加热的肿瘤相比，这种热应激还导致由gadd 153启动子驱动的TNF-α基因表达增加了3倍。在热效应不足以导致细胞死亡的周边区域也观察到了TNF-α基因表达。联合治疗在30天内强烈抑制了裸鼠肿瘤的生长，表明其在癌症治疗方面具有潜力。
