Development of vector specific to diffuse-type gastric cancer cells for peritoneal metastasis control

我们研究了GSDMB基因的启动子活性，该基因在弥漫性胃癌（GCs）中优先表达。该启动子在人间皮细胞系MeT-5A中作用较弱，而在6个弥漫性GC细胞系中的5个中作用较强。接下来构建GSDMB启动子驱动的hsvtk慢病毒载体。该载体对MeT-5A细胞无细胞毒性，而更昔洛韦（GCV）处理可杀死70%的弥散型gc来源的60As6细胞。然后我们用60As6细胞建立了腹膜转移控制小鼠模型。106个60As6细胞注射后，通过每周1次的GCV处理，持续30天，我们评估了该载体在体内的作用。gcv处理小鼠的存活率为67%，对照组为33%。

We investigated the promoter activity of the GSDMB gene, which was identified to be expressed preferentially in diffuse-type gastric cancers (GCs). This promoter was found to act weakly in human mesothelial cell line MeT-5A but strongly in 5 of 6 diffuse-type GC cell lines. We next constructed the GSDMB promoter-driven HSVtk-lentivirus vector. This vector showed no cytotoxicity in MeT-5A cells, whereas 70% of diffuse-type GC-derived 60As6 cells were killed by Ganciclovir (GCV) treatment. We then established a peritoneal-metastasis control mouse model using 60As6 cells. By GCV treatment only once a week for 30 days after i.p. of 106 60As6 cells, we evaluated in vivo effects of this vector. The survival rate of GCV-treated mice showed 67%, but that of control mice showed 33%.