Inhibition of 5-lipoxygenase triggers apoptosis in pancreatic cancer cells

Zhou,Guo-Xiong; Ding,Xiao-Ling; Wu,Sheng-Bao; Zhang,Hai-Feng; Cao,Wei; Qu,Li-Shuai; Zhang,Hong

doi:10.3892/or.2014.3650

Inhibition of 5-lipoxygenase triggers apoptosis in pancreatic cancer cells

Authors:
- Guo-Xiong Zhou
- Xiao-Ling Ding
- Sheng-Bao Wu
- Hai-Feng Zhang
- Wei Cao
- Li-Shuai Qu
- Hong Zhang
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Affiliations: Department of Gastroenterology, Affliliated Hospital of Nantong University, Jiangsu, Nantong 226001, P.R. China
Published online on: December 5, 2014 https://doi.org/10.3892/or.2014.3650
Pages: 661-668

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Abstract

The 5-lipoxygenase (5-LOX) pathway has been associated with a variety of inflammatory diseases including asthma, atherosclerosis, rheumatoid arthritis, cancer and liver fibrosis. Several classes of 5-LOX inhibitors have been identified, but only one drug, zileuton, a redox inhibitor of 5-LOX, has been approved for clinical use. In the present study, 5-LOX was found to be overexpressed not only in pancreatic cancer cell lines but also in tissue samples of patients suffering from pancreatic adenocarcinoma. There was a close correlation between the tumor expression levels of 5-LOX mRNA and protein and the clinicopathological patient characteristics including lymph node metastasis and TNM stage. Zileuton suppressed the proliferation of SW1990 cells in a concentration- and time‑dependent manner. In addition, zileuton induced SW1990 cells to undergo apoptosis and significantly decreased 5-LOX expression. The number of apoptotic cells, estimated by flow cytometry, Annexin V/PI assay, TUNEL staining and sub‑diploid population was significantly higher than that of the control. These results suggest that the level of 5-LOX expression was increased in pancreatic cancer tissues and may be related to lymph node metastasis and TNM stage.

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