ApoE-modified liposomes mediate the antitumour effect of survivin promoter-driven HSVtk in hepatocellular carcinoma
Authors: Chan Zhang
Chang Liu
Chaochao Wen
Fanxiu Meng
Chunyang Xu
Qin Qin
Tao Gong
Hongwei Zhang
Xiuli Mu
Gaopeng Li
Baofeng Yu
Na Zhao
Xiushan Dong
Qi Zhang
Gongqin Sun
Xi Wang
Lumei Wang
Yan Wei
Jun Xu
Rui Guo
Journal: Cancer Gene Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: Hepatocellular carcinoma; gene therapy; HSVtk/GCV; ApoE-modified liposomes; survivin promoter
Affiliations: Department of Biochemistry and Molecular Biology, Basic Medical College, Shanxi Medical University, Taiyuan, 030001, Shanxi, China., Department of Biological Sciences, The Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA, 15264, USA., Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI, 02881, USA., Department of General Surgery, Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China., Department of Haematology, Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China., Central Laboratory, Shanxi Provincial People's Hospital, Shanxi Medical University, Taiyuan, 030001, Shanxi, China., Department of General Surgery, Shanxi Dayi Hospital, Taiyuan, 030001, Shanxi, China. ., Department of General Surgery, Shanxi Dayi Hospital, Taiyuan, 030001, Shanxi, China., Department of Dermatology, Dong Guan People's Hospital, Dongguan, Guangdong, 523018, China. ., Department of Biochemistry and Molecular Biology, Basic Medical College, Shanxi Medical University, Taiyuan, 030001, Shanxi, China. .

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. 

Retracted: No

PubPeer comments:
 Figure 6D contains tumors that have identical elements. Could the authors explain what may have happened here? Original: ![file] Duplicate regions highlighted (some with minor differences): ![file] , 
 #1 I agree. With image inverted, Foresically clone detection looks like this: ![file] ,