Synergistic inhibitory effect of gamma-interferon and EGF on A431 cells

Addition of high concentrations (100ng/ml) of epidermal growth factor (EGF) to cultures of the epidermoid-carcinoma cell-line A431, which expresses high levels of the EGF receptor, resulted in 50 percent reduction in growth rate. At a lower level (10 ng/ml) of EGF no such inhibitory effect was observed. Addition of gamma-interferon at a concentration of 100 u/ml, but not alpha-interferon at the same concentration, inhibited the growth rate of A431 cells by 50 percent. Incubation of the cells in medium containing both 10 ng/ml of EGF and 1000 u/ml of gamma-interferon led to a complete growth arrest. After 48 hours this inhibition was not reversible and resulted in excessive cell-death after approximately seven days. The human lung cancer cell-line U-1752, which expresses low levels of the EGF receptor, was not inhibited by EGF even at high concentrations. Gamma-interferon did not increase the sensitivity of these cells to EGF. The results show that the modulating effect of gamma-interferon on EGF activity is variable and probably depends on cell line receptor concentration as well as the primary effect of EGF on different cells.