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，该基因被鉴定为在弥漫型胃癌（GC）中优先表达。发现该启动子在人间皮细胞系MeT-5A中作用较弱，但在6种弥漫型GC细胞系中的5种中作用较强。我们接下来构建了GSDMB启动子驱动的HSVtk-慢病毒载体。该载体在MeT-5A细胞中没有显示出细胞毒性，而70%的弥漫型GC衍生的60 As 6细胞被更昔洛韦（GCV）处理杀死。然后，我们使用60 As 6细胞建立了腹膜转移对照小鼠模型。通过GCV处理仅一周一次，持续30天，在106个60 As 6细胞的腹膜内注射后，我们评估了该载体的体内效应。GCV处理组小鼠的存活率为67%，而对照组小鼠的存活率为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%.