Reversal of the malignant phenotype of cervical cancer CaSki cells through adeno-associated virus-mediated delivery of HPV16 E7 antisense RNA.

Abstract

Human papillomavirus (HPV) infection is the most important risk factor for the development of cervical cancer. The oncogene E7 from high-risk HPV strains has the ability to immortalize epithelial cells and increase cellular transformation in culture. In this study, we explored the possibility of preventing cervical cancer growth by inhibiting HPV16 E7 expression through gene transfer of an antisense construct. A recombinant adeno-associated virus (rAAV) vector was chosen for the transfer, based on its transfection efficiency, in vivo stability, and lack of detectable pathology. In vitro transfer of an rAAV vector expressing antisense HPV16 E7 (AAV-HPV16E7AS) inhibited cell proliferation, induced apoptosis, reduced cell migration, and restrained in vivo proliferation of HPV16/HPV18-positive cervical cancer CaSki cells. These results indicate that down-regulation of HPV16 E7 with antisense RNA is beneficial in reducing the tumorigenicity of CaSki cells, and rAAV vectors ought to be a new efficient approach for delivering the expression of therapeutic genes.