[Gene therapy using cationic multilamellar liposomes containing human interferon-beta gene against renal cell
Yoichi Mizutani1, Hiroyuki Nakanishi, Tsuneharu Miki
1Department of Urology, Kyoto Prefectural University of Medicine.
Abstract:
The anticancer activity of cationic multilamellar liposomes containing human IFN-beta gene (IAB-1) against renal cell carcinoma (RCC) was examined. Concentrations of IFN-beta protein were measured by an enzyme-linked immunosorbent assay. The cytotoxic activity of IAB-1 against RCC cells and normal renal proximal tubule endothelial cells (RPTEC5899) was examined by the microculture tetrazolium dye assay. For the in vivo study, the NC65 RCC cell line was inoculated into severe combined immunodeficiency mouse. The RCC cells treated with IAB-1 secreted significant amounts of IFN-beta protein. Significant in vitro cytotoxic activity of IAB-1 against RCC cells was observed. In contrast, treatment of RCC cells with recombinant IFN-beta protein resulted in less cytotoxicity. No significant cytotoxicity was seen in RPTEC5899 cells. Apoptosis was observed in RCC cells treated with IAB-1. The size of NC65 RCC cancers transfected with IAB-1 in mice was significantly smaller than that receiving injection of empty liposomes or recombinant IFN-beta protein. These findings show that IAB-1 may have significant antitumor activity against RCC, and suggest its potential clinical application for gene therapy against RCC.
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