title: Effect of NS-398 on colon cancer cells.
abstract: OBJECTIVE
  To study the effect of NS-398, a selective cyclooxygenase-2 (COX-2) inhibitor, on invasion of colon cancer cell line HT-29 in vitro and to explore its mechanisms.
  
  
  METHODS
  Invasive behaviors of the malignant colon cancer cell line HT-29 were investigated in this study. Expressions of COX-2 and CD44v6 in HT-29 cells were detected by flow cytometry. Cellular survival rate was determined by MTT assay. The invasive capacity was quantified by a modified Boyden chamber model. Alterations of cytoskeleton component F-actin were observed by confocal laser scanning microscope.
  
  
  RESULTS
  Flow cytometry analysis showed that COX-2 was highly expressed in HT-29 cells. The invasive capability of HT-29 cells could be greatly inhibited by NS-398 at the experimental concentrations of 0.1, 1.0 and 10 micormol/L with an inhibitory rate of 22.74%, 42.35% and 58.61% (P<0.01), respectively. MTT assay showed that NS-398 at the experimental concentrations had no significant influence on cellular viability, indicating that such anti-invasive effects had no relationship with cytotoxicity. F-actin was mainly distributed around nuclei forming annular structure in HT-29 cells. After exposure to NS-398 of 10 micromol/L, the annular structure around nuclei disappeared and the fluorescence intensity of F-actin decreased obviously. Treatment with NS-398 could down-regulate the expression of CD44v6 as well.
  
  
  CONCLUSIONS
  NS-398 has anti-invasive effects on colon cancer HT-29 cells in vitro, which may be mediated by a novel mechanism of disruption of cytoskeleton. Down-regulation of CD44v6 expression may be related to alterations of cytoskeleton.
authors.affiliation: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China. xiaoqingjia@126.com
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Jia
authors.forename: Ning
authors.initials: N
authors.lastname: Zhong
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Han
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: Fan-Li
authors.initials: FL
authors.lastname: Meng
authors.forename: Shang-Zhong
authors.initials: SZ
authors.lastname: Zhang
mesh_terms: D000199:Actins / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003599:Cytoskeleton / Q000648:ultrastructure; D015536:Down-Regulation; D006023:Glycoproteins / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009578:Nitrobenzenes / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000199:Actins; C112697:CD44v6 antigen; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases