Zhuravel L. Functional analysis of beta-defensin-2 in malignant cells

The objective of investigation was analysis of beta-defensin-2 function in tumor cells. Using the transfection of two cell lines - HEK293 (human embryonic kidney) and 3LL (Lewis lung carcinoma) - with plasmids containing cDNA for mature and precursor forms of beta-defensin-2, two cell models with different levels of beta-defensin-2 expression have been developed. In experimental research carried on model HEK293 cell sublines, it has been shown that up-regulation of expression and intracellular accumulation of hBD-2 led to the loss of cell clonogenic capacity and more than three-fold decrease of their proliferative activity. Also it has been demonstrated that hBD-2 up-regulation correlated with decreased phosphorylation of ribosomal S6 protein. It has been found out that in 3LL cells transfected with vectors containing cDNA for mBD-2 with or without leader sequence, the expression of mBD-2 mRNA is down-regulated compared to parental cells and the cells transfected with blank vector. The down-regulationof mBD-2 expression in these cells is associated with elevated colony forming capacity and increased proliferation rate. The cells with suppressed mBD-2 expression transplantated to C57Bl/6 mice generated the tumors that possessed significantly higher growth rate than those that arise from wild-type 3LL cells or the cells transfected with blank vector (p<0.01). The data obtained allow to make a conclusion about potential supressor properties of beta-defensin-2 toward tumor cells.