THYMOSIN ALPHA-1 DOWN-REGULATES THE GROWTH OF HUMAN NONSMALL CELL LUNG-CANCER CELLS IN-VITRO AND IN-VIVO

The effect of thymosin alpha1 (THNalpha1) and it, NH2-terminal fragmen t (THN1-14) and COOH-terminal fragment (THN15-28) on non-small cell lu ng cancer (NSCLC) growth was evaluated. Using an anti-THNalpha1 antibo dy, receptors we identified on NSCLC cells that were pretreated with 1 0(-6) M THNalpha1. [H-3]Arachidonic acid was readily taken up by NSCLC cells and THNalpha1 significantly increased the rate of arachidonic a cid release. THN1-15 slightly stimulated but THN15-28 and THNbeta4 did not alter arachidonic acid release from NCI-H1299 cells. In clonogeni c growth assays in vitro, THNalpha1 (10(-6) M) significantly decreased NSCLC colony number whereas THN1-14, THN15-28, and THNbeta4 were less potent. Using growth assays in vivo, THNalpha1 (10 mug s.c./day) but not THN1-14, THN15-28, or THNbeta4 inhibited significantly NSCLC xenog raft formation in nude mice. These data suggest that biologically acti ve THNalpha1 receptors are present on NSCLC cells and that native THNa lpha1 inhibits the growth of human NSCLC.