Effect of NS-398 on colon cancer cells.

Abstract

AIM:

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.

CONCLUSION:

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: Xiao-Qing Jia, Ning Zhong, Li-Hui Han, Jing-Hua Wang, Ming Yan, Fan-Li Meng, Shang-Zhong Zhang
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 11 Issue 3 Pg. 353-6 (Jan 21 2005) ISSN: 1007-9327 [Print] United States
• PMID: 15637743 (Publication Type: Journal Article)

Chemical References

• Actins
• CD44v6 antigen
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Glycoproteins
• Hyaluronan Receptors
• Isoenzymes
• Membrane Proteins
• Nitrobenzenes
• Sulfonamides
• N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases

Topics

• Actins (drug effects)
• Colonic Neoplasms (metabolism, pathology)
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (pharmacology)
• Cytoskeleton (ultrastructure)
• Down-Regulation
• Glycoproteins (metabolism)
• HT29 Cells
• Humans
• Hyaluronan Receptors (metabolism)
• Isoenzymes (metabolism)
• Membrane Proteins
• Neoplasm Invasiveness (prevention & control)
• Nitrobenzenes (pharmacology)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Sulfonamides (pharmacology)