title: Effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on lung cancer: roles of cyclooxygenase-2.
abstract: We examined the effects of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the lung cancer cell lines PC-9, LA-1 and A549. In addition, we examined if the effects of the cytokines on the cell lines are mediated by activation of cyclooxygenase (COX)-2. The three cell lines did not constitutively produce either G-CSF or GM-CSF. G-CSF did not influence cell growth in the three cell lines, while GM-CSF increased cell growth in the A549 and LA-1 lines. G-CSF and GM-CSF dose-dependently decreased cell death in the three cell lines. RT-PCR demonstrated GM-CSF receptor expression in the three lung cancer cell lines, whereas the G-CSF receptor exists only in the PC-9 line. We suggest that G-CSF might rescue the tumor cells from cytotoxicity due to serum deprivation through cellular pathways independent of the G-CSF receptor. G-CSF and GM-CSF increased cyclooxygenase-2 (COX-2) expression in PC-9 and LA-1 cells whereas they decreased COX-2 expression in A549 cells. The COX-2 inhibitor NS-398 increased cell death in PC-9 and LA-1 cells, whereas it decreased cell death in A549 cells. PC-9 and LA-1 clones transfected with sense G-CSF- or GM-CSF showed an increase in COX-2 expression, while COX-2 expression was decreased in transfected A549 clones. COX-2 expression was increased in anti-sense G-CSF- and GM-CSF-transfected A549 clones. Thus, although COX-2 activation seems to induce different biological behavior depending on the cell type, we propose that G-CSF and GM-CSF might accelerate tumor progression by directly regulating COX-2 expression, independently of an autocrine mechanism.
authors.affiliation: Department of Internal Medicine, Kochi Medical School, Nankoku, Kochi 783-8505, Japan. uemuray@med.kochi-u.ac.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Uemura
authors.forename: Makoto
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hideshi
authors.initials: H
authors.lastname: Nakata
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kubota
authors.forename: Tsuyako
authors.initials: T
authors.lastname: Saito
authors.forename: Kentaro
authors.initials: K
authors.lastname: Bandobashi
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Taguchi
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D009578:Nitrobenzenes / Q000494:pharmacology; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000906:Antibodies; D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D051546:Cyclooxygenase 2