Anti-tumor effect of oncolytic herpes simplex virus G47delta on human nasopharyngeal carcinoma  

作　　者：Jia-Ni Wang Pan Hu Mu-Sheng Zeng Ren-Bin Liu 

机构地区：[1]Breast Cancer Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P. R. China [2]State Key Laboratory of Oncology in South China, Guangzhou, Guangdong 510060, P. R. China [3]Research Department, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.

出　　处：《Chinese Journal of Cancer》2011年第12期831-841,共11页

基　　金：supported by grants from the NationalScience Foundation of China (30672410);theGuangdong Natural Science Foundation (06104599)

摘　　要：Oncolytic herpes simplex virus (HSV) can replicate in and kill cancer cells without harming normal tissue. G47Δ is a third-generation HSV vector. In this study, the therapeutic effects of G47Δ on human nasopharyngeal carcinoma (NPC) were determined in vitro and in vivo. The human NPC cell lines CNE-2 and SUNE-1, primary normal nasopharyngeal epithelial cells (NPECs), and immortalized nasopharyngeal cells NP-69 and NPEC2/Bmi1 were infected with G47Δ at different multiplicities of infection (MOIs). The survival of infected cells was observed daily. Two subcutaneous models of NPC were established with CNE-2 and SUNE-1 in Balb/c nude mice. G47Δ or virus buffer as control was injected into the subcutaneous tumors. Tumor size was measured twice a week, and animals were euthanized when the diameter of their tumors exceeded 18 mm or when the animals appeared moribund. For the NPC cell lines CNE-2 and SUNE-1, more than 85% and 95% of cells were killed on day 5 after G47Δ infection at MOI = 0.01 and MOI = 0.1, respectively. Similar results were observed for an immortalized cell line NPEC2/Bmi-1. A moderate effect of G47Δ was also found on another immortalized cell line NP-69, of which only 27.7% and 75.9% of cells were killed at MOI = 0.01 and MOI = 0.1, respectively. On the contrary, there was almost no effect observed on NPECs. The in vivo experiments showed that tumors in mice in the G47Δ-treated group regressed completely, and the mice exhibited much longer survival time than those in the control groups. Our results suggest that the potential therapeutic effects of G47Δ would be applicable for treatment of NPC patients in the future.Oncolytic herpes simplex virus （HSV） can replicate in and kill cancer cells without harming normal tissue. G47△ is a third-generation HSV vector. In this study, the therapeutic effects of G47△ on human nasopharyngeal carcinoma （NPC） were determined in vitro and in vivo. The human NPC cell lines CNE-2 and SUNE-1, primary normal nasopharyngeal epithelial cells （NPECs）, and immortalized nasopharyngeal cells NP-69 and NPEC2/Bmil were infected with G47△ at different multiplicities of infection （MOIs）. The survival of infected cells was observed daily. Two subcutaneous models of NPC were established with CNE-2 and SUNE-1 in Balb/c nude mice. G47A or virus buffer as control was injected into the subcutaneous tumors. Tumor size was measured twice a week, and animals were euthanized when the diameter of their tumors exceeded 18 mm or when the animals appeared moribund. For the NPC cell lines CNE-2 and SUNE-1, more than 85% and 95% of cells were killed on day 5 after G47△ infection at MOI = 0.01 and MOI = 0.1, respectively. Similar results were observed for an immortalized cell line NPEC2/Bmi- 1. A moderate effect of G47△ was also found on another immortalized cell line NP-69, of which only 27.7% and 75.9% of cells were killed at MOI = 0.01 and MOI = 0.1, respectively. On the contrary, there was almost no effect observed on NPECs. The in vivo experiments showed that tumors in mice in the G47△-treated group regressed completely, and the mice exhibited much longer survival time than those in the control groups. Our results suggest that the potential therapeutic effects of G47△ would be applicable for treatment of NPC patients in the future.

关 键 词：单纯疱疹病毒载体 鼻咽癌细胞 抗肿瘤 永生细胞株 感染细胞 治疗效果 体内实验 缓冲区控制 

分 类 号：S659.1[农业科学—果树学] TN248.1[农业科学—园艺学]