Effect of Adenovirus Mediated Fusion Gene System Driven by KDR Promoter on Proliferation and Apoptosis of Colorectal Cancer Cells

Objective 　To study the effect of adenovirus (Ad) mediated double suicide gene driven by KDR promoter on proliferation and apoptosis of human colorectal cancer LOVO cells. Methods 　The KDR producing cells LOVO and the KDR nonproducing cells LS174 T were infected by the AdEasy2KDR2CDg2 lyTK respectively, followed by t reatment with 52FC and GCV. killing effect s of this suicide gene system on colorectal cancer cells were evaluated. Moreover, the dist ribution of cell cycle was detected by flow cytomet ric assay and pathological character of cells was observed by elect ron microscopy. Results 　The infection rate of the resultant recombinant Ad ( rAd) to all the cells had not apparently different, and it in2 creased gradually with the addition of multiple of infection (MOI) of Ads. The infected cells exhibited dif2 ferent sensibility to the two prodrugs : LOVO cells infected with rAd were sensitive highly to the pro2 drugs, but the LS174 T cells infected with rAd appeared to be unsensitive to the two prodrugs ( P <0. 001) . The killing effect of CD/ TKfusion gene on the target cells was much st ranger than that of each single suicide gene ( P < 0. 001), and they all had considerable bystander effect . In addition, the cell cycle of LOVO cells was arrested at S phase and morphologic features of apoptosis and necrosis in LOVO cells were displayed via elect ron microscopy. Conclusion 　The CD/ TK fusion gene system cont rolled by KDR promoter has selectively killing effect on the KDR2CDglyTKexpressing LOVO cells, the mechanism of which may involve the halting the cell cycles and cytotoxic necrosis and apoptosis of cell.