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

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 using the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene system for HCC that can be further developed for future clinical trials.
PMID: 31306654 [PubMed - as supplied by publisher]

Source: Experimental Cell Research - July 11, 2019 Category: Cytology Authors: Liu C, Wen C, Wang X, Wei Y, Xu C, Mu X, Zhang L, Wang X, Tian J, Ma P, Meng F, Zhang Q, Zhao N, Yu B, Gong T, Guo R, Wang H, Xie J, Sun G, Li G, Zhang H, Qin Q, Xu J, Dong X, Wang L Tags: Exp Cell Res Source Type: research