Rapamycin inhibits constitutive p70s6k phosphorylation, cell proliferation, and colony formation in small cell lung cancer cells.
The serine/threonine kinase p70s6k was found to be constitutively phosphorylated in H 69, H 345, and H 510 small cell lung cancer cells as judged by the retarded electrophoretic mobility of both isoforms of this kinase. Pretreatment of H 69, H 345, and H 510 cells with the potent immunosuppressant rapamycin led to p70s6k 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 concentrations to those required for inducing dephosphorylation of p70s6k. Furthermore, rapamycin markedly reduced the basal colony forming ability of H 69, H 345, and H 510 cells in semisolid media. Thus, constitutively phosphorylated/active p70s6k plays an important role in promoting the growth of small cell lung cancer cells. Furthermore, the rapamycin-sensitive p70s6k pathway may provide a novel target for therapeutic intervention in small cell lung cancer.
Seufferlein
T
T
Imperial Cancer Research Fund, London, United Kingdom.
Rozengurt
E
E
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007536:Isomerism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011090:Polyenes / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus
D000903:Antibiotics, Antineoplastic; D011090:Polyenes; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus