Gene Therapy with Cytosine Deaminase and Endostatin Fusion Gene Mediated by Endothelial Progenitor Cells in Hepatomas

Yue-Lin Zhang; Tan-Yang Zhou; Jing Ai; Sheng-Qun Chen; Feng Chen; Chun-Hui Nie; Xin-Hua Chen; Guan-Hui Zhou; Hong-Liang Wang; Tong-Yin Zhu; Bao-Quan Wang; Zi-Niu Yu; Li Jing; Li-Ming Wu; Shu-Sen Zheng; Jun-Hui Sun

doi:10.2147/CMAR.S245998

Gene Therapy with Cytosine Deaminase and Endostatin Fusion Gene Mediated by Endothelial Progenitor Cells in Hepatomas

Cancer Manag Res. 2020 Apr 30:12:3023-3031. doi: 10.2147/CMAR.S245998. eCollection 2020.

Authors

Yue-Lin Zhang^#^{1

2}, Tan-Yang Zhou^#^{1

2}, Jing Ai^#³, Sheng-Qun Chen^#^{1

2}, Feng Chen⁴, Chun-Hui Nie^{1

2}, Xin-Hua Chen^{1

2}, Guan-Hui Zhou^{1

2}, Hong-Liang Wang^{1

2}, Tong-Yin Zhu^{1

2}, Bao-Quan Wang^{1

2}, Zi-Niu Yu^{1

2}, Li Jing^{1

2}, Li-Ming Wu^{1

2}, Shu-Sen Zheng^{1

2}, Jun-Hui Sun^{1

2}

Affiliations

¹ Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, People's Republic of China.
² Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, People's Republic of China.
³ Eye Centre, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, People's Republic of China.
⁴ Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: Gene-targeting therapy provides a novel therapeutic approach for tumor treatment using genetically modified endothelial progenitor cells (EPCs) as cellular carriers. This study applied EPCs armed with cytosine deaminase (CD) and endostatin (ES) fusion gene in liver cancer to explore its therapeutic effect.

Materials and methods: EPCs from heart blood of male BALB/c nude mice were cultured and transfected with CD and ES fusion gene. Subsequently, these genetically modified cells were injected into mice bearing hepatoma through their tail veins. The tumor volumes and cell apoptosis were followed up.

Results: Tumor volume in the group injected CD/ES-EPCs greatly decreased. The positive rate of VEGF and CD31 in the tumor tissue was lowest in the CD/ES-EPC group. Furthermore, the number of apoptotic cells was highest in the CD/ES-EPC group.

Conclusion: The EPCs transfected with CD/ES inhibited tumor growth and preferentially induced tumor cell apoptosis, providing a novel methodology for cancer-targeting therapy.

Keywords: cytosine deaminase; endostatin; endothelial progenitor cell; gene-targeting therapy; hepatoma; transfection.