Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka, Japan.
Cancer Lett. 2010 Aug 28;294(2):178-86. doi: 10.1016/j.canlet.2010.01.034. Epub 2010 Feb 16.
To overcome the limited clinical efficacy of conditionally replicative adenoviruses (CRAds), we investigated the effects of combination therapy with gemcitabine (GEM) and the hTERT-promoter-dependent CRAd (hTERT-CRAd), Ad5/3hTERTE1. This combination therapy exhibited enhanced cytotoxic effects on pancreatic cancer both in vitro and in vivo. Furthermore, we revealed that this enhancement effect was due to the multiple bidirectional interactions between hTERT-CRAd and GEM. The GEM-sensitizing effect of E1 expression derived from hTERT-CRAd, and the enhancement effect by GEM on hTERT promoter activity which led to the increase of adenovirus E1 and viral infectivity. This combination therapy may be a promising therapeutic approach for pancreatic cancer.
为了克服条件复制型腺病毒（CRAds）的临床疗效有限的问题，我们研究了吉西他滨（GEM）联合 hTERT 启动子依赖性 CRAd（hTERT-CRAd），即 Ad5/3hTERTE1 的治疗效果。该联合疗法在体外和体内均对胰腺癌显示出增强的细胞毒性作用。此外，我们揭示了这种增强作用是由于 hTERT-CRAd 和 GEM 之间的多种双向相互作用所致。来自 hTERT-CRAd 的 E1 表达的 GEM 增敏作用，以及 GEM 对 hTERT 启动子活性的增强作用，导致腺病毒 E1 和病毒感染力增加。这种联合治疗可能是胰腺癌有前途的治疗方法。
