| Summary: | 碩士 === 國防醫學院 === 生物化學研究所 === 88 === In our previous study, we found that the Epstein-Barr virus nuclear antigene-1 (EBNA1) could act as a transforming suppressor of the HER-2/neu oncogene. In order to substantiate the application of EBNA1 in human cancer gene therapy, we injected intraperitoneally ovarian cancer cells SKOV3.ip1、SKOV3 and 2774, respectively, into nude mice and established the tumor bearing mouse model. Then, we used our newly developed SP/DOPE liposome to deliver EBNA1 gene for the treatment of the ovarian tumor-bearing nude mice for one year. The results showed that the EBNA1 could inhibit the cell proliferation of ovarian cancer SKOV3, although the treatment was not very efficient for SKOV3.ip1 that may be due to low transfection efficiency. Therefore, an arginine-rich protein protamine was used to modify the SP/DOPE/EBNA1 DNA complex for improving the transfection efficiency into the ovarian cancer cells. It revealed that there were 2-fold increase in the transfection efficiency for SKOV3.ip1 and 2774 cells by comparing with that of unmodified SP/DOPE/EBNA1 DNA complex. In addition, a low toxicity to nude mice was observed in the safety test, including the biochemical profile and toxicity test. Taken together, these results showed that the protamine-modified liposome/EBNA1 DNA complex can improve the transfection efficiency for SKOV3.ip1 and 2774 cells and may provide a therapeutic benefit for HER-2/neu-overexpressing human cancers.
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