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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Treatment of hepatocellular carcinoma by AdAFPep/rep, AdAFPep/p53, and 5-fluorouracil in mice.
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Treatment of hepatocellular carcinoma by AdAFPep/rep, AdAFPep/p53, and 5-fluorouracil in mice.

机译：通过AdAFPep / rep，AdAFPep / p53和5-氟尿嘧啶在小鼠中治疗肝细胞癌。

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Although conditionally replicable adenovirus (CRAd) has been used in the clinical treatment of hepatocellular carcinoma (HCC), it suffers from the inherent drawback of having relatively low antitumor activity. Here, we have sought to overcome this drawback. First, we combined CRAd (AdAFPep/Rep) driven by alpha-fetoprotein enhancer/promoter (AFPep) with a replication-incompetent adenovirus carrying a p53 transgene that is also driven by AFPep. The synergism of this combination produced a significantly improved tumoricidal effect on the human HCC cell line Hep3B, which has a relatively short doubling time in comparison with other human HCC cell lines, through the transactivation of p53 by early region 1A transcribed by AdAFPep/Rep. This synergistic interaction was augmented by the addition of a subtumoricidal dose (0.5 microg/mL) of 5-fluorouracil (5-FU), which enhanced p53 expression and facilitated the release of virions from tumor cells. When relatively large (10-mm-diameter) Hep3B tumors grown in nude mice were injected with the two viruses in combination, they showed significantly impaired growth in comparison with those treated with each virus separately. The growth suppression effect of the virus combination was enhanced by a low dose (600 microg) of 5-FU. Survival of the tumor-bearing mice treated with these three agents was significantly longer than that of control mice. Moreover, the tumor completely disappeared with the repeated injection of these agents. CONCLUSION: This combination strategy holds promise for the treatment of relatively large and rapidly growing HCCs that may be encountered clinically.
机译：尽管条件复制型腺病毒（CRAd）已用于肝细胞癌（HCC）的临床治疗，但其固有的缺点是抗肿瘤活性较低。在这里，我们试图克服这一缺陷。首先，我们将由甲胎蛋白增强子/启动子（AFPep）驱动的CRAd（AdAFPep / Rep）与带有p53转基因的无复制能力的腺病毒结合，该腺病毒也由AFPep驱动。该组合的协同作用通过由AdAFPep / Rep转录的早期区域1A对p53的反式激活，对人HCC细胞系Hep3B产生了显着改善的杀肿瘤效果，与其他人HCC细胞系相比，其具有相对较短的倍增时间。通过添加杀伤剂量（0.5 microg / mL）的5-氟尿嘧啶（5-FU）增强了这种协同相互作用，该剂量增强了p53的表达并促进了病毒粒子从肿瘤细胞中的释放。当在裸鼠中生长的相对较大（直径10毫米）的Hep3B肿瘤同时注射两种病毒时，与分别用每种病毒治疗的相比，它们显示出明显受损的生长。低剂量（600微克）的5-FU增强了病毒组合的生长抑制作用。用这三种药物治疗的荷瘤小鼠的存活期明显长于对照小鼠。此外，通过重复注射这些药物，肿瘤完全消失。结论：这种联合策略有望为临床上可能遇到的相对较大且快速增长的肝癌进行治疗。

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