溶瘤疱疹病毒表达的病毒融膜糖蛋白抗食管癌的实验研究

为了探讨溶瘤疱疹病毒表达病毒融膜糖蛋白对食管癌细胞的杀伤效果，采用基因酶切技术构建携带GALV．fus基因的致融性溶瘤疱疹病毒Synco-l和Synco-2以及非致融性溶瘤疱疹病毒Baco－1，通过体内外实验观察三种病毒对食管癌细胞Eca－109的杀伤效果。结果发现，Synco－1和Synco－2能引起食管癌细胞融合，有效地杀灭食管癌细胞。体外实验Synco－1和Synco－2能分别使Eca-109细胞存活率降低至28％和25％，体内实验能使实体肿瘤体积明显缩小，接种4周后，均能使小鼠70％的癌细胞完全消失，其杀伤食管癌细胞的效果明显强于非致融性溶瘤疱疹病毒Baco－1。实验结果提示，溶瘤疱疹病毒通过表达病毒融膜糖蛋白能显著增强其抗肿瘤效果，Synco－1和Synco－2有可能成为治疗食管癌的有效工具。

Studies on the Therapy of Esophageal Cancer with An Oncolytic Virus Incorporating Fusogenic Membrane Glycoproteins

This study aims to determine the anti-esophageal cancer effect of oncolytic herpesvirus expressing fusogenic membrane glycoprotein. We constructed Synco-1 and Synco-2 by inserting the gene of gibbon ape leukemia virus envelope fusogenic membrane glycoprotein （GALV.fus） into an oncolytic herpes simplex virus with an enforced ligation procedure. We also constructed Baco-1 without GALV.fus gene. The ability of these oncolytic viruses to kill esophageal cancer cells Eca-109 in vitro and in vivo was assessed. Subsequent in vitro and in vivo studies showed that expression of GALV.fus in the context of an oncolytic virus significantly enhances the antitumor effect of the virus. In vitro, the syncytial plaques after Synco-1 and Synco-2 infection were founded. Synco-1 and Synco-2 killed Eca-109 tumor cells more effectively than Baco-1 both in vitro and in vivo. In vitro, the percentages of cells that survived after infection of Synco-1 and Synco-2 were 28% and 25%. In vivo, 70% of the animals were tumor free at the 4th week after Synco-1 and Synco-2 administration, respectively. These results suggest that expression of fusogenic membrane glycoprotein by these fusogenic oncolytic herpesviruses can enhance the antitumor effects. Synco-1 and Synco-2 may provide a novel therapy against esophageal cancer.