Effect of NS398 on metastasis-associated gene expression in a human colon cancer cell line

AIM: To investigate the effect of NS398 on the metastasis-associated gene expression in LoVo colorectal cancer cells. METHODS: LoVo cells were treated with NS398 at the concentration of 100 mu mol/L for 24 and 48 h respectively. Total RNA was extracted with TRIzol reagents and reverse transcribed with Superscript II and hybridized with cDNA microarray (containing oncogenes, tumor suppressor genes, signal transduction molecules, adhesive molecules, growth factors, and ESTs) fabricated in our laboratory. After normalization, the ratio of gene expression of NS398 treated to untreated LoVo cells was either 2-fold up or 0.5-fold down was defined as the differentially expressed genes. Semi-quantitative RT-PCR was used to validate the microarray results. RESULTS: Among the 447 metastasis-associated genes, 9 genes were upregulated and 8 genes were downregulated in LoVo cells treated with NS398 for 24 h compared to untreated cells. While 31 genes were upregulated and 14 genes were downregulated in LoVo cells treated with NS398 for 48 h. IGFBP-5, PAI-2, JUN, REL, BRCA1, and BRCA2 might be the new targets of NS398 in treatment of colorectal cancer. CONCLUSION: NS398 might exert its anti-metastasis effect on colorectal cancer by affecting several metastasis-associated gene expression. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.