- 期刊
Tumor 5-Lipoxygenase Expression Correlates with Gastric Cancer Metastasis and Its Selective Inhibitor Induces Cancer Cell Apoptosis
並列摘要
AIM: To study the expression status of 5-lipoxygenase (5-LOX) in gastric cancer tissues and investigate the effect of 5-LOX selective inhibitor AA861 on human gastric cancer AGS cell line. METHODS: 5-LOX mRNA and protein expression in gastric tumors were analyzed by RT-PCR and immunohistochemistry, respectively. AGS cells were treated with AA861, and cell viability was surveyed by microculture tetrazolium test. Apoptosis-related changes in morphology were observed by transmission electron microscopy. Apoptotic cell level was estimated by TUNEL and flow cytometric assays. The effect of AA861 on cellular 5-LOX expression was investigated by RT-PCR and immunocytochemistry. RESULTS: The expression of 5-LOX mRNA and protein was detected in gastric cancer tissues. The positive rates of 5-LOX mRNA and protein expression in gastric cancer were 76.7% and 72.5%, respectively, which were significantly higher than 16.7% and 23.3% in non-tumor tissues (P＜0.05). There was a close correlation between the tumor expression of 5-LOX protein and the clinicopathological characteristics including lymph node metastasis and TNM stages (P＜0.05). AA861 suppressed proliferation of AGS cells in a concentration and time-dependent manner. Morphological features of apoptosis, including cell shrinkage, nuclear condensation and fragmentation, and formation of apoptotic bodies, were observed from AA861-treated cells. After exposure to AA861, the apoptotic cell level estimated by TUNEL staining was significantly elevated. Typical sub-diploid population was also detected by flow cytometric analysis. There was no significant difference in the expression level of 5-LOX between treated group and control group. CONCLUSION: The level of 5-LOX expression was increased in gastric cancer tissues and had a close relationship with lymph node metastasis and TNM stages. AA861 induced AGS cells to undergo apoptosis but had no effect on 5-LOX expression.
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