A novel Golgi protein (GOLPH2)-regulated oncolytic adenovirus exhibits potent antitumor efficacy in hepatocellular carcinoma

// Yigang Wang 1 , Tao Liu 1, * , Panpan Huang 1, * , Hongfang Zhao 1 , Rong Zhang 1 , Buyun Ma 1 , Kan Chen 1 , Fang Huang 4 , Xiumei Zhou 1 , Caixia Cui 3 , Xinyuan Liu 1, 2 1 Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China 2 Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China 3 Otorhinolaryngology Head and Neck Surgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, PR China 4 School of Public Health, Zhejiang University, Hangzhou 310058, China * These authors have contributed equally to this work Correspondence to: Yigang Wang, e-mail: wangyigang43@163.com Xinyuan Liu, e-mail: xyliu@sibs.ac.cn Keywords: GOLPH2, hepatocellular carcinoma, oncolytic adenovirus, anticancer capacity Received: February 10, 2015 Accepted: April 10, 2015 Published: April 23, 2015 ABSTRACT 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.