12-HETE facilitates cell survival by activating the integrin-linked kinase/NF-κB pathway in ovarian cancer

• Main Authors: Liu Q, Tan W, Che J, Yuan D, Zhang L, Sun Y, Yue X, Xiao L, Jin Y
• Format: Article
• Language: English
• Published: Dove Medical Press 2018-11-01
• Series: Cancer Management and Research
• Subjects: 12-HETE; ILK; Apoptosis; NF-κB; ovarian cancer
• Online Access: https://www.dovepress.com/12-hete-facilitates-cell-survival-by-activating-the-integrin-linked-ki-peer-reviewed-article-CMAR

Qian Liu,1,* Wenhua Tan,1,* Jianhua Che,1,* Dandan Yuan,1 Liying Zhang,1 Yuhong Sun,1 Xiaolong Yue,2 Lei Xiao,3 Yuxia Jin1 1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China; 2Department of Medical Oncology, Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China; 3Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China *These authors contributed equally to this work Background: The dysfunction of cell apoptosis is an important event in the progression of cancer, and the growth of cancer cells is negatively regulated by cell apoptosis. In different types of cancers, inhibition of cellular apoptosis is often observed in the cancerous tissue, and increased resistance to apoptosis is a hallmark of cancer. Although previous studies have shown that 12-lipoxygenase (12-LOX)/12-hydroxyeicosatetraenoic acid (12-HETE) is activated and upregulated in different types of cancers, the consequences of 12-LOX/12-HETE upregulation and its precise roles in the survival of ovarian carcinoma cells are still unknown.Methods: MTT assays, caspase activity assays, lactate dehydrogenase (LDH) assays, and Western blot analysis were the methods used in this study.Results: In our study, we found that 12-HETE, a major metabolic product of arachidonic acid using 12-LOX catalysis, inhibited cell apoptosis in a dose-dependent manner and that the effects of 12-HETE on cell apoptosis were mediated by the integrin-linked kinase (ILK) pathway. Moreover, the downstream target of 12-HETE-activated ILK was nuclear factor kappa-B (NF-κB) in ovarian carcinoma. The inhibitory effects of 12-HETE on cell apoptosis were attenuated by the inhibition of the NF-κB pathway.Conclusion: These results indicate that 12-HETE participates in the inhibition of cell apoptosis by activating the ILK/NF-κB pathway, implying an important underlying mechanism that promotes the survival of ovarian cancer cells. Keywords: 12-HETE, ILK, apoptosis, NF-κB, ovarian cancer