Effects of an adenoviral vector containing a suicide gene fusionon growth characteristics of breast cancer cells

Abstract

The herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) and the cytosine deaminase/5-fluorocytosine (CD/5-FC) systems have been widely applied in suicide gene therapy for cancer. Although suicide gene therapy has been successfully used in vitro and in vivo studies, the number of studies on the effects of recombinant adenoviruses (Ads) containing suicide genes on target cancer cells is limited. The aim of this study was to examine whether recombinant Ads containing the CD/TK fusion gene affect cell proliferation of breast cancer cells in vitro. In the present study, we explored the use of a recombinant adenoviral vector to deliver the CD/TK fusion gene to the breast cancer cell line MCF-7. We found that the recombinant adenoviral vector efficiently infected MCF-7 cells. Western blot analysis revealed that CD and TK proteins are expressed in the infected cells. The infected breast cancer cells did not show any significant changes in morphology, ultrastructure, cell growth, and cell-cycle distribution compared to the uninfected cells. This study revealed that the Ad-vascular endothelial growth factor promoter (VEGFp)-CD/TK vector is non-toxic to MCF-7 cells at the appropriate titer. Our results indicate that it is feasible to use a recombinant adenoviral vector containing the CD/TK fusion gene in suicide gene therapy to target breast cancer cells.