J. Cancer Mol. 2: 227-233, 2006

[Research Paper]

Tumor 5-Lipoxygenase Expression Correlates with Gastric Cancer Metastasis and Its Selective Inhibitor Induces Cancer Cell Apoptosis

Lai-Yu Zou, Jian-Ying Li, Feng-Lin Chen, Zhi-Xin Chen, and Xiao-Zhong Wang

Department of Gastroenterology, Union Hospital of Fujian Medical University, Fuzhou, Fujian Province, China

Abstract:

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.