Format

Send to

Choose Destination
Cancer Gene Ther. 2019 Oct 23. doi: 10.1038/s41417-019-0145-3. [Epub ahead of print]

ApoE-modified liposomes mediate the antitumour effect of survivin promoter-driven HSVtk in hepatocellular carcinoma.

Author information

1
Department of Biochemistry and Molecular Biology, Basic Medical College, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
2
Department of Biological Sciences, The Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA, 15264, USA.
3
Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI, 02881, USA.
4
Department of General Surgery, Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
5
Department of Haematology, Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
6
Central Laboratory, Shanxi Provincial People's Hospital, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
7
Department of General Surgery, Shanxi Dayi Hospital, Taiyuan, 030001, Shanxi, China. junxuty@163.com.
8
Department of General Surgery, Shanxi Dayi Hospital, Taiyuan, 030001, Shanxi, China.
9
Department of Dermatology, Dong Guan People's Hospital, Dongguan, Guangdong, 523018, China. zbwlm2002@163.com.
10
Department of Biochemistry and Molecular Biology, Basic Medical College, Shanxi Medical University, Taiyuan, 030001, Shanxi, China. shanxiyangchengdg@163.com.

Abstract

Hepatocellular carcinoma (HCC) is a prevalent malignant tumour with high global morbidity and mortality associated with its multiple aetiologies, poor prognosis, resistance to chemotherapeutic drugs and high rate of recurrence. Here, we evaluated a gene therapy strategy that targets 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. Apolipoprotein E (ApoE)-modified liposomes were used for targeted gene delivery to the tumour tissue, and the survivin promoter was used to drive HSVtk expression in HCC cells. Our results showed that the survivin promoter was specifically activated in tumour cells, and HSVtk was expressed selectively in tumour cells. In combination with GCV treatment, HSVtk expression resulted in the inhibition of HCC cell proliferation via enhanced apoptosis. In addition, tail vein injection of ApoE-HSVtk significantly suppressed the growth of xenograft tumours through an apoptosis-dependent pathway and extended the survival time of tumour-bearing mice. In summary, this study illustrates an effective cancer-specific gene therapy strategy for HCC that can be further developed for future clinical trials.

PMID:
31645678
DOI:
10.1038/s41417-019-0145-3

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center