Small‐molecule inhibition of prostaglandin E receptor 2 impairs cyclooxygenase‐associated malignant glioma growth

• DOI: 10.1111/bph.14622
• Publication Date: 2019-02-14T08:35:46Z
• Authors: Jiange Qiu; Qianqian Li; Katherine A. Bell; Xue Yao; Yifeng Du; Erik Zhang; Jane J. Yu; Ying Yu; Zhi Shi; Jianxiong Jiang
• Keywords: Prostaglandin E2 receptor

Background and Purpose An up‐regulation of COX‐2 in malignant gliomas causes excessive synthesis PGE 2 , which is thought to facilitate brain tumour growth invasion. However, downstream receptor subtype (i.e., EP 1 –EP 4 ) directly contributes COX activity‐promoted glioma remains largely unknown. Experimental Approach Using a publicly available database from The Cancer Genome Atlas research network, we compared the expression signalling‐associated genes human lower grade glioblastoma multiforme (GBM) samples. Kaplan–Meier analysis was performed determine relationship between their survival probability. A time‐resolved FRET method used identify that mediates COX‐2/PGE ‐initiated cAMP signalling GBM cells. Taking advantage recently identified novel selective bioavailable brain‐permeable small‐molecule antagonist, studied effect pharmacological inhibition on cell vitro vivo. Key Results key Gα s ‐coupled pathways Inhibition receptors reduced activity‐driven proliferation, invasion, migration caused cycle arrest at G0–G1 apoptosis Glioma vivo also substantially decreased by post‐treatment with an antagonist both subcutaneous intracranial models. Conclusion Implications Taken together, our results suggest via increases potential cells might represent therapeutic target for GBM.