title: Nitric oxide inhibits gastric cancer cell growth through the modulation of the Akt pathway.
abstract: Nitric oxide (NO) is involved in a number of physiological and pathological processes. As an important biological mediator, NO has been the focus of cancer study for its function in tumorigenesis, tumor progression and death. The effects of NO on tumor cells are multifaceted, but many details underlying these effects are not yet well understood. In this study, we demonstrate that NO directly suppresses the growth of BGC-823 cells by inducing G0/G1 phase arrest in a dose- and time-dependent manner. We also reveal that G0/G1 arrest results from the NO-induced disruption of the cell cycle balance, which is mediated by the up-regulation of p21waf1/cip1 and the down-regulation of cyclin D1 and E and PCNA. Exposure of BGC-823 cells to various sodium nitroprusside (SNP) concentrations for 24 h or to 1 mmol/l SNP for various times resulted in a marked decrease in the level of phospho-Akt and increase in the level of phospho-ERK. In brief, the NO-induced cell growth suppression and G0/G1 arrest are mediated through the regulation of cell cycle-related proteins, which may depend on the inactivation of Akt signaling. This may be one mechanism through which NO inhibits gastric cancer cell growth.
authors.affiliation: School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu, PR China. sangjianrong@yahoo.com.cn
authors.forename: Jianrong
authors.initials: J
authors.lastname: Sang
authors.forename: Yongchang
authors.initials: Y
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Tao
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D020030:Nitric Oxide Donors; D018809:Proliferating Cell Nuclear Antigen; D019938:Cyclin D1; D009599:Nitroprusside; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases