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

Cancer Gene Therapy volume 27, pages 754–767 (2020)Cite this article

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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.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (30901821, 81172136), International Science and Technology Cooperation Project of Shanxi provincial Key R&D Program (201703D421023,201703D421023), Natural Science Foundation of Shanxi province (2015011113), Shanxi Youth Science and Technology Research Fund (201801D221059, 201801D221069), the Fund for Shanxi “1331 Project” Key Subjects Construction and the Fund for Shanxi Key Subjects Construction.

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  1. These authors contributed equally: Xiuli Mu, Xi Wang

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Basic Medical College, Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Xiuli Mu, Xi Wang, Yan Wei, Chaochao Wen, Qi Zhang, Chang Liu, Chan Zhang, Fanxiu Meng, Na Zhao, Tao Gong, Rui Guo, Gongqin Sun & Baofeng Yu

  2. Department of Biological Sciences, The Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA, 15264, USA

    Chunyang Xu

  3. Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI, 02881, USA

    Gongqin Sun

  4. Department of General Surgery, Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Gaopeng Li

  5. Department of Haematology, Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Hongwei Zhang

  6. Central Laboratory, Shanxi Provincial People’s Hospital, Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Qin Qin

  7. Department of General Surgery, Shanxi Dayi Hospital, Taiyuan, 030001, Shanxi, China

    Jun Xu & Xiushan Dong

  8. Department of Dermatology, Dong Guan People’s Hospital, Dongguan, Guangdong, 523018, China

    Lumei Wang

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Correspondence to Jun Xu, Lumei Wang or Baofeng Yu.

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Mu, X., Wang, X., Wei, Y. et al. ApoE-modified liposomes mediate the antitumour effect of survivin promoter-driven HSVtk in hepatocellular carcinoma. Cancer Gene Ther 27, 754–767 (2020). https://doi.org/10.1038/s41417-019-0145-3

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