LIPOSOME-MEDIATED IN-VIVO E1A GENE-TRANSFER SUPPRESSED DISSEMINATION OF OVARIAN-CANCER CELLS THAT OVEREXPRESS HER-2 NEU/

The HER-2/neu proto-oncogene is frequently amplified or overexpressed in many different types of human cancers, a phenomenon that has been s hown to correlate with shorter survival time and lower survival rate i n ovarian cancer patients, We previously reported that increased HER-2 /neu expression led to more severe malignancy and increased metastatic potential in animal models and that the adenovirus 5 E1A gene repress ed HER-2/nue gene expression at transcriptional level and was able to suppress tumor growth when stably transfected into human ovarian cance r SKOV-3 cells which overexpress HER-2/neu. To investigate whether the E1A gene may be used as a therapeutic agent for HER-2/neu-overexpress ing human cancers in living hosts, we first developed tumor-bearing mi ce by injecting SKOV-3 cells that overexpress HER-2/neu intraperitonea ly into female nu/nu mice, Five days later, rye used cationic liposome s to directly deliver the E1A gene into adenocarcinomas that developed in the peritoneal cavity and an the mesentery of the mice that receiv ed the SKOV-3 cell injection, We found that liposome-mediated E1A gene transfer significantly inhibited growth and dissemination of ovarian cancer cells that overexpress HER-2/neu in the treated mice; about 70% of these mice survived at least 365 days, whereas all the control mic e that did not receive the gene therapy developed severe tumor symptom s and died within 160 days, The results suggest that liposome-mediated E1A gene transfer may serve as an effective therapy for human ovarian cancers that overexpress HER-2/neu by directly targeting the HER-2/ne u oncogene.