OncoTargets and Therapy (Aug 2019)
GPX2 suppression of H2O2 stress regulates cervical cancer metastasis and apoptosis via activation of the β-catenin-WNT pathway
Abstract
Yingxin Wang,1,* Penglong Cao,1,* Mohammed Alshwmi,1 Nan Jiang,2 Zhen Xiao,3 Fengquan Jiang,1 Juebin Gu,1 Xiaonan Wang,1 Xiaoye Sun,1 Shijun Li11Clinical Laboratory, The First Hospital of Dalian Medical University, Dalian 116011, People’s Republic of China; 2Department of Pathology, The First Hospital of Dalian Medical University, Dalian 116011, People’s Republic of China; 3Department of Gynecology, The First Hospital of Dalian Medical University, Dalian 116011, People’s Republic of ChinaCorrespondence: Shijun LiClinical Laboratory, The First Hospital of Dalian Medical University, 222 Zhongshan Road, Xigang District, Dalian 116011, People’s Republic of ChinaTel +86 411 8611 0497Email [email protected]*These authors contributed equally to this workBackground: Increasing evidence suggests that glutathione peroxidase 2 (GPX2) plays important roles in the tumorigenesis and progression of various human cancers, such as colorectal carcinomas and lung adenocarcinomas. However, the role of GPX2 in cervical cancer is unclear. In this study, we identified the role of GPX2 in cervical cancer tissues and cell lines.Materials and methods: The basal mRNA and protein expression of GPX2 in cervical cancer cells and a series of key molecules in the epithelial to mesenchymal transition (EMT) and WNT/β-catenin pathways were examined via real time fluorescence quantitative PCR (qRT-PCR) and Western blot assays. The biological phenotype of the cervical cancer cell lines was detected by the cloning formation and transwell assays, and intracellular reactive oxygen species (ROS) levels were detected by flow cytometry. Finally, the GPX2 expression level in 100 clinical cervical tissues was examined by immunohistochemistry.Results: We found that GPX2 was highly expressed in cervical cancer tissues compared to normal individuals and promoted the proliferation and metastasis of cervical cancer cells, and this promotion correlated with the activation of EMT and WNT/β-catenin signaling in vitro. GPX2 was determined to reduce apoptotic damage by reducing hydroperoxides. According to the characteristics and verification of GPX2, this series of phenotypes is clearly related to oxidative stress in cells. Furthermore, we verified that GPX2 was highly expressed in cervical cancer tissues and promoted the metastasis of cervical cancer.Conclusion: In summary, we found that GPX2 was highly expressed in cervical cancer cells and promoted the proliferation and metastasis of cervical cancer by affecting oxidative stress. Our study provides a new target for the clinical treatment of cervical cancer.Keywords: GPX2, reactive oxygen species, epithelial to mesenchymal transition, metastasis
