tailieunhanh - Báo cáo khoa học: Adenine nucleotides inhibit proliferation of the human lung adenocarcinoma cell line LXF-289 by activation of nuclear factor jB1 and mitogen-activated protein kinase pathways

Extracellular nucleotides have a profound role in the regulation of the pro-liferation of diseased tissue. We studied how extracellular nucleotides regu-late the proliferation of LXF-289 cells, the adenocarcinoma-derived cell line from human lung bronchial tumor. ATP and ADP strongly inhibited LXF-289 cell proliferation. | ễFEBS Journal Adenine nucleotides inhibit proliferation of the human lung adenocarcinoma cell line LXF-289 by activation of nuclear factor kB1 and mitogen-activated protein kinase pathways Rainer Schafer1 Roland Hartig2 Fariba Sedehizade1 Tobias Welte3 and Georg Reiser1 1 Institut fur Neurobiochemie Otto-von-Guericke-Universitat Medizinische Fakultejt Magdeburg Germany 2 Institut fur Immunologie Otto-von-Guericke-Universitat Medizinische Fakultat Magdeburg Germany 3 Klinik fur Pneumologie Medizinische Hochschule Hannover Germany Keywords cell cycle progression mitogen-activated protein kinase nuclear factor-KB1 P2Y receptors phosphatidylinositol-3-kinase protein kinase C Correspondence G. Reiser Otto-von-Guericke-Universitat Magdeburg Medizinische Fakultat Institut fuur Neurobiochemie Leipziger Str. 44 39120 Magdeburg Germany Fax 49 391 6713097 Tel 49 391 6713088 E-mail . Received 4 February 2006 revised 12 June 2006 accepted 16 June 2006 doi Extracellular nucleotides have a profound role in the regulation of the proliferation of diseased tissue. We studied how extracellular nucleotides regulate the proliferation of LXF-289 cells the adenocarcinoma-derived cell line from human lung bronchial tumor. ATP and ADP strongly inhibited LXF-289 cell proliferation. The nucleotide potency profile was ATP ADP ATPyS UTP UDP whereas . p y-methy-lene-ATP 2 3 -ơ- 4-benzoylbenzoyl -ATP AMP and UMP were inactive. The nucleotide potency profile and the total blockade of the ATP-mediated inhibitory effect by the phospholipase C inhibitor U-73122 clearly show that P2Y receptors but not P2X receptors control LXF-289 cell proliferation. Treatment of proliferating LXF-289 cells with 100 pM ATP or ADP induced significant reduction of cell number and massive accumulation of cells in the S phase. Arrest in S phase is also indicated by the enhancement of the antiproliferative effect of ATP by coapplication