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KMID : 0613820070170070996
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Journal of Life Science
2007 Volume.17 No. 7 p.996 ~ p.1001
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Analysis of Differentially Expressed Genes by Sulindac Sulfide in Human Colorectal Cells
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Shin Seung-Hwa
Kim Jong-Sik
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Abstract
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To investigate whether sulindac, sulindac sulfone, and sulindac sulfide could affect cancer cell viabilities, human colorectal HCT116 cells were treated with 10 μM of each NSAID. Among treated NSAIDs, sulindac sulfide dramatically decreased the cell viabilities detected by MTS and the cytotoxic effect showed dose-dependent manner. To understand the molecular mechanism of cell death in response to sulindac sulfide treatment, we performed oligo DNA microarray analysis. We found that 23 genes were up-regulated more than 2 folds, whereas 33 genes were down-regulated more than 2 folds by treatment of 10 μM sulindac sulfide. Among the up-regulated genes, we selected 3 genes (NAG-1, DDIT3, PCK2) and performed RT-PCR and quantitative real-time PCR to confirm microarray data. The results of RT-PCR and real-time PCR were highly accorded with those of microarray experiment. As NAG-1 is well-known gene as tumor suppressor, we detected changes of NAG-1 expression by 10 μM of sulindac, sulindac sulfone, and sulindac sulfide. The results of RT-PCR and quantitative real-time PCR indicated that sulindac sulfide was the strongest inducer of NAG-1 among treated NSAIDs. This result implies that induction of NAG-1 by sulindac sulfide plays important role in cell death of colorectal cancer. Overall, we speculate that these results may be helpful in understanding the molecular mechanism of the cancer chemoprevention by sulindac sulfide in human colorectal cancer.
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KEYWORD
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Colorectal cancer, chemoprevention, NSAID, DNA microarray, gene expression
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