Wang Yigang, Liu Tao, Huang Panpan, Zhao Hongfang, Zhang Rong, Ma Buyun, Chen Kan, Huang Fang, Zhou Xiumei, Cui Caixia, Liu Xinyuan
Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China.
School of Public Health, Zhejiang University, Hangzhou 310058, PR China.
Oncotarget. 2015 May 30;6(15):13564-78. doi: 10.18632/oncotarget.3769.
Golgi apparatus is the organelle mainly functioning as protein processing and secretion. GOLPH2 is a resident Golgi glycoprotein, usually called GP73. Recent data displayed that GOLPH2 is a superb hepatocellular carcinoma (HCC) marker candidate, and even its specificity is better than liver cancer marker AFP. Oncolytic adenoviruses are broadly used for targeting cancer therapy due to their selective tumor-killing effect. However, it was reported that traditionally oncolytic adenovirus lack the HCC specificity. In this study, a novel dual-regulated oncolytic adenovirus GD55 targeting HCC was first constructed based on our cancer targeted gene-viral therapeutic strategy. To verify the targeting and effectiveness of GOLPH2-regulated oncolytic adenovirus GD55 in HCC, the anticancer capacity was investigated in HCC cell lines and animal model. The results proved that the novel GOLPH2-regulated GD55 conferred higher adenovirus replication and infectivity for liver cancer cells than oncolytic adenovirus ZD55. The GOLPH2-regulated GD55 exerted a significant grow-suppressing effect on HCC cells in vitro but little damage to normal liver cells. In animal experiment, antitumor effect of GD55 was more effective in HCC xenograft of nude mice than that of ZD55. Thus GOLPH2-regulated GD55 may be a promising oncolytic virus agent for future liver cancer treatment.
高尔基体是主要负责蛋白质加工和分泌的细胞器。GOLPH2是一种高尔基体驻留糖蛋白，通常称为GP73。最近的数据显示，GOLPH2是一种出色的肝细胞癌（HCC）标志物候选物，甚至其特异性优于肝癌标志物甲胎蛋白（AFP）。溶瘤腺病毒因其选择性杀瘤作用而被广泛用于靶向癌症治疗。然而，据报道，传统的溶瘤腺病毒缺乏肝癌特异性。在本研究中，基于我们的癌症靶向基因-病毒治疗策略，首次构建了一种新型的靶向肝癌的双调控溶瘤腺病毒GD55。为了验证GOLPH2调控的溶瘤腺病毒GD55在肝癌中的靶向性和有效性，在肝癌细胞系和动物模型中研究了其抗癌能力。结果证明，新型的GOLPH2调控的GD55比溶瘤腺病毒ZD55赋予肝癌细胞更高的腺病毒复制和感染性。GOLPH2调控的GD55在体外对肝癌细胞具有显著的生长抑制作用，但对正常肝细胞几乎没有损伤。在动物实验中，GD55在裸鼠肝癌异种移植模型中的抗肿瘤效果比ZD55更有效。因此，GOLPH2调控的GD55可能是未来肝癌治疗中一种有前景的溶瘤病毒药物。
