Prostaglandin E2 upregulates β1 integrin expression via the E prostanoid 1 receptor/nuclear factor κ-light-chain-enhancer of activated B cells pathway in non-small-cell lung cancer cells.

The prostaglandin E-2 (PGE(2)) E prostanoid (EP)1 receptor shown to be associated with lung cancer cell invasion. However, the mechanism of EP1 receptor-mediated cell migration remains to be elucidated. beta 1 integrin is an essential regulator of the tumorigenic properties of non-small-cell lung carcinoma (NSCLC) cells. To date, little is known regarding the association between the EP1 receptor and beta 1 integrin expression. The present study investigated the effect of EP1 receptor activation on beta 1 integrin expression and cell migration in NSCLC cells. A total of 34 patients with clinical diagnosis of NSCLC and 10 patients with benign disease were recruited for the present study. The expression levels of the EP1 receptor and beta 1 integrin expression were studied in resected lung tissue using immunohistochemistry. A statistical analysis was performed using Stata se12.0 software. The effects of PGE(2), EP1 agonist 17-phenyl trinor-PGE(2) (17-PT-PGE(2)) and the nuclear factor kappa-B (NF-kappa B) inhibitor on beta 1 integrin expression were investigated on A549 cells. The expression of beta 1 integrin and the phosphorylation of NF-kappa B-p65 Ser536 was investigated by western blot analysis. Cell migration was assessed by a transwell assay. The results demonstrated that beta 1 integrin and EP1 receptor expression exhibited a positive correlation of evident significance in the 44 samples. The in vitro migration assay revealed that cell migration was increased by 30% when the cells were treated with 5 mu M 17-PT-PGE(2) and that the pre-treatment of beta 1 integrin monoclonal antibody inhibited 17-PT-PGE(2)-mediated cell migration completely. PGE(2) and 17-PT-PGE(2) treatment increased beta 1 integrin expression. RNA interference against the EP1 receptor blocked the PGE(2)-mediated beta 1 integrin expression in A549 cells. Treatment with 17-PT-PGE(2) induced NF-kappa B activation, and the selective NF-kappa B inhibitor pyrrolidin-edithiocarbamate inhibited 17-PT-PGE(2)-mediated beta 1 integrin expression. In conclusion, the present study indicated that the PGE(2) EP1 receptor regulates beta 1 integrin expression and cell migration in NSCLC cells by activating the NF-kappa B signaling pathway. Targeting the PGE(2)/EP1/beta 1 integrin signaling pathway may aid in the development of new therapeutic strategies for the prevention and treatment of this type of cancer.