INHIBITION OF HUMAN COLON-CANCER MALIGNANT-CELL BEHAVIOR AND GROWTH BY ANTISENSE EPIDERMAL GROWTH-FACTOR RECEPTOR EXPRESSION VECTOR

Human colon cancer cells utilize the epidermal growth factor (EGF) fam ily of growth factors and the receptor for these growth factors (EGFR) in sustaining their malignant phenotype. Disrupting EGFR expression b y expressing antisense EGFR RNA (through transfection with an appropri ate antisense EGFR expression vector under metallothionein promoter co ntrol) downregulated the malignant behavior of human colon cancer Mose r cells and blocked the ability of exogenous EGF in stimulating malign ant cell behavior. The antiproliferative effect of antisense EGFR expr ession vector was determined in three human colon cancer cell lines (M oser, HCT116 and HT29 possessing different biological properties and r ate of proliferation) in an in vitro therapeutic setting using an anti sense EGFR expression vector under the control of a viral promoter. Di fferent degree of inhibition was achieved for each cell line after one dose of antisense treatment. The differences in the antiproliferative effect observed may be due to differences in the rate of proliferatio n and/or recovery from antisense effect, and the differences in transf ection efficiency among the cell lines.