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J Gastroenterol Hepatol ; 22(12): 2324-9, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17559385

ABSTRACT

BACKGROUND AND AIM: Non-steroidal anti-inflammatory drugs (NSAIDs) can prevent colorectal cancer (CRC), but their effect is limited. Recent studies have shown the involvement of 15-lipoxygenase-1 (15-LOX-1) in NSAID-induced apoptosis in colorectal carcinoma cells. We evaluate whether 15-LOX-1 expression influences the sensitivity of NSAID-induced apoptosis in CRCs. METHODS: In 22 CRC surgical samples from NSAID users who had been constant for more than 5 years and 28 CRC surgical samples from NSAID non-users, the expressions of 15-LOX-1, cyclooxygenase-2 (COX-2), beta-catenin, and p53 were analyzed using immunohistochemistry. TUNEL assay was also performed for samples. The effects of the transient transfection of 15-LOX-1 cDNA on indomethacin-induced apoptosis were certified in HCT-116 cells. The effects of adding 13-S-hydroxyoctadecadinoic acid (13-S-HODE) on indomethacin-induced apoptosis were also examined in HCT-116 cells. The levels of apoptosis were determined by the analysis of the floating-cells ratio and DNA gel electrophoresis. RESULTS: The expression of 15-LOX-1 on CRCs from NSAID users was significantly decreased compared with those from NSAID non-users; however, the expressions of other molecules were not significantly different between two groups. The levels of TUNEL scoring in samples from NSAID users were similar to those from NSAID non-users. Indomethacin (100 microM) induced less apoptosis in mocked cells, whereas the same concentrations of indomethacin enhanced the level of apoptosis in 15-LOX-1-transfected cells. 13-S-HODE also increased the level of indomethacin-induced apoptosis in cells. CONCLUSION: Results suggest that 15-LOX-1 expression may be one of the mechanisms which enhance the sensitivity to NSAID-induced apoptosis in CRCs from patients who are treated with the compounds.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Apoptosis/drug effects , Arachidonate 15-Lipoxygenase/metabolism , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/pathology , Aged , Cyclooxygenase 2/metabolism , Drug Screening Assays, Antitumor , Female , HCT116 Cells , Humans , Immunohistochemistry , In Situ Nick-End Labeling , Indomethacin , Linoleic Acids/pharmacology , Male , Tumor Suppressor Protein p53/metabolism , beta Catenin/metabolism
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