STC1 promotes cell apoptosis via NF-κB phospho-P65 Ser536 in cervical cancer cells

Abstract

// Xi Pan 1, 2, 3 , Binyuan Jiang 1, 2 , Jianhao Liu 4 , Juan Ding 3 , Yuehui Li 1, 2 , Ruili Sun 1, 2 , Li Peng 1, 2 , Changfei Qin 1, 2 , Shujuan Fang 1, 2 and Guancheng Li 1, 2 1 The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410008, China 2 Cancer Research Institute, Central South University, Changsha 410078, China 3 Xiangya Third Hospital, Central South University, Changsha 410078, China 4 School of Pharmaceutical Sciences of Central South University, Changsha 410078, China Correspondence to: Guancheng Li, email: ligc61@csu.edu.cn Keywords: stanniocalin-1 (STC1), cell apoptosis, cervical cancer, NF-κB, phospho-P65 (Ser536) Received: November 22, 2016     Accepted: March 11, 2017     Published: May 05, 2017 ABSTRACT Stanniocalin-1 (STC1) is a secreted glycoprotein hormone and involved in various types of human malignancies. Our previous studies revealed that STC1 inhibited cell proliferation and invasion of cervical cancer cells through NF-κB P65 activation, but the mechanism is poorly understood. In our studies, we found overexpression of STC1 promoted cell apoptosis while silencing of STC1 promoted cell growth of cervical cancer. Phospho-protein profiling and Western blotting results showed the expression of NF-κB related phosphorylation sites including NF-κB P65 (Ser536), IκBα, IKKβ, PI3K, and AKT was altered in STC1-overexpressed cervical cancer cells. Moreover, PI3K inhibitor LY294002, AKT-shRNA and IκBα-shRNA could decrease the protein content of phospho-P65 (Ser536), phospho-IκBα, phospho-AKT and phospho-IKKβ while increasing the level of P65 compared to STC1 overexpression groups in cervical cancer cells. Also, PI3K inhibitor LY294002, AKT-shRNA and IκBα-shRNA elevated the percentage of apoptosis and suppressed the G1/S transition in those cells. Additionally, STC1 level was decreased in cervical cancer, especial in stage II and III. The results of immunohistochemistry for the cervical cancer microarray showed that a lower level of STC1, phospho-PI3K and P65 protein expression in tumor tissues than that in normal tissues, and a higher level of phospho-P65 protein expression in tumor tissues, which is consistent with the results of the Western blotting. These data demonstrated that STC1 can promote cell apoptosis via NF-κB phospho-P65 (Ser536) by PI3K/AKT, IκBα and IKK signaling in cervical cancer cells. Our results offer the first mechanism that explains the link between STC1 and cell apoptosis in cervical cancer.