Effect of endothelial progenitor cells modified by suicide gene on growth of hepatocellar carcinoma in orthotopic tumor-transplanted mice / 肿瘤

ABSTRACT

Objective: To investigate the suppression effect of mouse marrow-derived endothelial progenitor cells (EPCs) modified by cytosine deaminase (CD) gene and enzyme prodrug 5-fluorocytosine (5-Fc) on the growth of hepatocellar carcinoma in orthotopic H22 cell-transplanted mice. Methods: The EPCs were transfected by lentiviral vector carrying CD gene (plenti6.3-EGFP-CD) using Polybrene technique. The mouse hepatoma H22 cells were treated by the supernatant of EPCs carrying CD gene and 5-Fc, and then the number and morphology of the cells were observed under an inverted microscope. C57BL/6 mice bearing orthotopic transplanted H22 hepatocellar carcinoma were treated by EPCs carrying CD gene and 5-Fc. The volume of tumor in mice was monitored by magnetic resonance imaging, and the apoptosis in tumor was tested by terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling (TUNEL) assay. The expression of CD protein in the transplanted tumor was identified by Western blotting. Results: The proliferation of H22 cells treated by the supernatant of EPCs carrying CD gene combined with 5-Fc was significantly reduced. Compared with the control, the tumor growth in the hepatocellular carcinoma orthotopic-transplantation mouse models treated by EPCs carrying CD gene and 5-Fc was inhibited to (47.29±5.81)% (P < 0.05), and the apoptosis index of tumor cells was markedly increased [(39.98±5.13)%]. Conclusion: The EPCs modified by CD gene combined with 5-Fc administration can effectively inhibit the proliferation of the mouse orthotopic transplanted hepatocellular carcinoma, and induce the apoptosis of tumor cells. Copyright © 2014 by TUMOR.