Combined liposome-mediated cytosine deaminase gene therapy with radiation in killing rectal cancer cells and xenografts in athymic mice

Abstract

Purpose: The aim of this study was to assess the antitumor efficacy of combination of cytosine deamise (CD) suicide gene theraphy with radiation and to grope for new therapeutic strategy for local recurrent rectal cancer. Experimental Design: HR-8348 cell line of human rectal cancer was used to assess efficiency of transfection with plasmid pEGFP-N1 and PXJ41-CD. The cells were exposed to radiation followed by liposome-mediated transfection. Cell inhibition assay was done with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Antitumor efficacy of combined liposome-mediated CD suicide gene therapy with radiation was determined by treatment of nude mice bearing HR-8348 cancer cell xenograft. Results: The efficiency of liposome-mediated CD gene transaction can be improved by radiation. With radiation at 2,4,6, and 8 Gy, the efficiency of liposome-mediated transfection increased from 21.3% to 62.2%, 78.0%, 83.2%, and 87.8%, respectively. CD expression was enhanced as well. Cancer cell inhibition experiment showed that combined liposome-mediated CD gene therapy with radiation had much stronger antitumor effect. With HR-8348 tumor xenograft model, suppression of tumor xenograft was observed. Compared with control group, tumor volume was inhibited by 81.5%, 48.5%, and 37.4%, respectively, in the combined CD/5-fluorocytosine with radiation group, CD/5-fluorocytosine group, and radiation group and the wet weight of tumor was decreased by 80%, 41.7%, and 37.7%, respectively. Conclusion: These findings suggested that combination of liposome-mediated CD gene therapy with radiation is a safer and efficient anticancer method. Its therapeutic efficacy may meet clinical treatment on local recurrent rectal cancer. © 2005 American Association for Cancer Research.