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Selective Cytotoxic Effect of Dual Tumor-targeting Oncolytic Adenovirus MD55 on Tumor and Normal Cells in Vitro
Wei-Yun Wang 1,2 , Jin-Fa Gu2, Pin Dai1, Tian Xiao2, Xin Cao2, Xin-Yuan Liu2*
1School of Life Science, East China Normal University, Shanghai 200062, China; 2Institute of Biochemistry and Cell Biology, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Abstract: A dual tumor-targeting oncolytic adenovirus (MD55) was constructed by molecular cloning and homologous recombination. The replication ability of MD55 virus in different cell lines was analyzed. Cytotoxic effects of the MD55 virus on tumor and normal cell lines were detected by crystal violet staining and MTT assay. After infected by virus, the expressions of E1A and PARP proteins in different cell lines were analyzed by Western blot. Results showed that MD55 displayed specific E1A expression in MN/CA9- positive cancer cell lines SW620 and OSRC-2. The proliferation ability and cytotoxic effect of MD55 virus became very low in normal cells, but almost equal to that of ZD55 in MN/CA9-positive cells. MD55 might induce apoptosis in SW620 and OSRC-2 cells but not in normal cells. The results suggest that MD55 has specific cytotoxicity in MN/CA9-positive cancer cells and more safety for normal cells in comparison with ZD55. It may be a good vector for cancer gene-virus therapy.