In lung cancers the Notch signaling may function as an oncogene or a tumor suppressor depending on the tumor cell types. In this study we examined the expression of Notch receptors in the human lung adenocarcinoma cell lines A549 and SPC-A-1. We over-expressed the active form of Notch1 (NIC) in A549 cells by constitutive transfection to evaluate the effects of the Notch signaling on lung adenocarcinoma cells. Our results showed that over-expression of NIC in A549 cells inhibited the growth of A549 cells through induction of cell cycle arrest. Moreover, over-expression of NIC inhibited the colony-forming activity of A549 cells when cultured in methylcellulose medium, and their ability to form tumors in nude mice. These data suggest that the Notch signaling may function as a tumor inhibitor in human lung adenocarcinoma cells.