Golgi membrane protein GP73 modified-liposome mediates the antitumor effect of survivin promoter-driven HSVtk in hepatocellular carcinoma

// Fanxiu Meng 1, * , Lina Zhang 1, * , Chunyang Xu 2 , Qi Zhang 1 , Yongfang Li 1 , Yingmin Zhang 1 , Na Zhao 1 , Baofeng Yu 1 , Rui Guo 1 , Hailong Wang 1 , Jun Xie 1 , Gongqin Sun 1, 3 , Gaopeng Li 4 , Jun Xu 4 , Qin Qin 5 and Xiushan Dong 6 1 Department of Biochemistry and Molecular Biology, Basic Medical Science, Shanxi Medical University, Taiyuan, Shanxi, China 2 Department of Biological Sciences, The Dietrich School of Arts and Sciences, University Of Pittsburgh, Pittsburgh, PA, USA 3 Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI, USA 4 Department of General Surgery, Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan, Shanxi, China 5 Central Laboratory, Shanxi Provincial People's Hospital, Shanxi Medical University, Taiyuan, Shanxi, China 6 Department of General Surgery, Shanxi Dayi Hospital, Taiyuan, Shanxi, China * These authors contributed equally to this work Correspondence to: Baofeng Yu, email: shanxiyangchengdg@163.com Jun Xu, email: junxuty@163.com Keywords: hepatocellular carcinoma; gene therapy; HSVtk/GCV; GP73; apoptosis Received: July 29, 2017      Accepted: October 28, 2017      Published: January 02, 2018 ABSTRACT Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide, and there is currently no effective therapeutic strategy in clinical practice. Gene therapy has great potential for decreasing tumor-induced mortality but has been clinically limited because of the lack of tumor-specific targets and insufficient gene transfer. The study of targeted transport of therapeutic genes in HCC treatment seems very importance. In this study, we evaluated a gene therapy approach targeting HCC using the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene system in HCC cell lines and in an in vivo human HCC xenograft mouse model. GP73-modified liposomes targeted gene delivery to the tumor tissue, and the survivin promoter drove HSVtk expression in the HCC cells. Our results showed that the survivin promoter was specifically activated in tumor cells and HSVtk was expressed selectively in tumor cells. Combined with GCV treatment, HSVtk expression resulted in suppression of HCC cell proliferation via enhancing apoptosis. Moreover, tail vein injection of GP73-HSVtk significantly suppressed the growth of xenograft tumors through an apoptosis-dependent pathway and extended the survival of tumor-bearing mice without damaging the mice liver functions. Taken together, this study demonstrates an effective cancer-specific gene therapy strategy for HCC that can be further developed for future clinical trials.