RAPAMYCIN INHIBITS CONSTITUTIVE P70(S6K) PHOSPHORYLATION, CELL-PROLIFERATION, AND COLONY FORMATION IN SMALL-CELL LUNG-CANCER CELLS

The serine/threonine kinase p70(s6k) was found to be constitutively ph osphorylated in H 69, H 345, and H 510 small cell lung cancer cells as judged by the retarded electrophoretic mobility of both isoforms of t his kinase. Pretreatment of H 69, H 345, and H 510 cells with the pote nt immunosuppressant rapamycin led to p70(s6k) dephosphorylation in a concentration-dependent manner; half-maximum and maximum effects were achieved at 0.3 and 3 nM rapamycin, respectively. Rapamycin inhibited growth of H 69, H 345, and H 510 cells in liquid culture at similar co ncentrations to those required for inducing dephosphorylation of p70(s 6k). Furthermore, rapamycin markedly reduced the basal colony forming ability of H 69, H 345, and H 510 cells in semisolid media. Thus, cons titutively phosphorylated/active p70(s6k) plays an important role in p romoting the growth of small cell lung cancer cells. Furthermore, the rapamycin-sensitive p70(s6k) pathway may provide a novel target for th erapeutic intervention in small cell lung cancer.