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

Abstract

Background: Gene-targeting therapy provides a novel therapeutic approach for tumor treatment using genetically-modified endothelial progenitor cells (EPCs) as cellular carriers. To study the therapeutic effect of EPCs armed with cytosine deaminase (CD) and endostatin (ES) fusion gene in liver cancer. Methods: EPCs derived from heart blood of mice were cultured and transfected with CD and ES fusion gene. EPCs, CD/ES, and CD/ES-EPCs were injected through their tail veins into mice with hepatoma, respectively. Subsequently, the in vivo tumor volumes were observed by MRI. Findings: Tumor volumes in the group injected CD/ES-EPCs were found to be smaller than other groups receiving other treatments. Also, VEGF and apoptotic tumor cells in the tumor tissues were detected after infusion of the cells into the mice. The results showed that the VEGF-positive rate was lowest and the number of apoptotic cells was highest in the CD/ES-EPCs group. Interpretation: The EPCs transfected with CD/ES inhibited tumor growth and preferentially induced tumor cell apoptosis. Thus, this treatment strategy might open a novel avenue for cancer-targeting therapy. Funding Statement: The present work was funded by Zhejiang Provincial Natural Science Foundation of China (Grant No.LZ18H180001), National S&T Major Project of China (NO.2018ZX10301201)，National Natural Science Foundation of China (Grant No.81371658), The Key Research Development Program of Zhejiang province (Grant No.2018C03018) and Key Science and Technology Program of Zhejiang province(No.WKJ-ZJ-1923). Declaration of Interests: The authors declare no potential conflict of interest. Ethics Approval Statement: All experimental procedures of the study were approved by our Institutional Animal Use and Care Committee. Mouse hepatocarcinoma model, aged 6 weeks, was provided by the Experimental Animal Center, College of Medicine, Zhejiang University. All experiments in this study were performed in agreement with the Guidelines for the Welfare of Animals in Experimental Neoplasia and approved our Institutional Animal Use and Care Committee.