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The EP 4 antagonist, L‐161,982, induces apoptosis, cell cycle arrest, and inhibits prostaglandin E2‐induced proliferation in oral squamous carcinoma Tca8113 cells
Author(s) -
Li Xiaohui,
Yang Bo,
Han Guoxu,
Li Weizhong
Publication year - 2017
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12572
Subject(s) - prostaglandin e2 receptor , cell growth , prostaglandin e2 , cancer research , cell cycle , apoptosis , mapk/erk pathway , cell cycle checkpoint , receptor , biology , chemistry , signal transduction , endocrinology , medicine , microbiology and biotechnology , agonist , biochemistry
Background Recent studies suggest that cyclooxygenase 2 (COX‐2) inhibitors may enhance the toxic effects of anticancer drugs on tumor cells, including oral squamous cell carcinoma (OSCC), but its long‐term use can cause side effects such as stomach ulcers and myocardial infarction. Our aim was to investigate proliferative effects of a downstream product of COX‐2, prostaglandin E2 (PGE2), in human oral squamous carcinoma cell line Tca8113 and explore the effects of PGE2 receptors, especially EP4 receptor, on the growth of Tca8113 cells. Methods To evaluate the effects of PGE2 and EP receptors on Tca8113 cells, CCK8 assay, Western blotting, cell cycle analysis, and apoptosis assay were performed. Results We found that the EP4 receptor agonist, PGE1‐OH, could mimick PGE2 rescued the inhibitory effect of celecoxib and induced cell growth via ERK phosphorylation, and the EP4 receptor antagonist, L‐161,982, completely blocked PGE2‐stimulated ERK phosphorylation and proliferation of Tca8113 cells. Furthermore, L‐161,982 may induce apoptosis and block cell cycle progression at s phase by upregulating Bax and p21 protein levels and by downregulating Bcl‐2, CDK2, and cyclin A2 protein levels. Conclusions Our results indicate that EP4 receptor mediates PGE2‐induced cell proliferation through ERK signaling, and inhibition of EP4 receptor may represent an alternative therapeutic strategy for the prevention and treatment of OSCC.