Inhibition of Ep3 attenuates migration and promotes apoptosis of non-small cell lung cancer cells via suppression of TGF-β/Smad signaling.

Non-small cell lung cancer (NSCLC) is the most common cause of cancer-associated mortality worldwide. Prostaglandin E2 (PGE2) regulates various biological processes, including invasion, proliferation and apoptosis. E-prostanoid 3 (Ep3) is a PGE2 receptor, and the functional role of Ep3 in the progression of NSCLC remains unresolved. The present study investigated the effects of Ep3 in A549 cells and explored the underlying molecular mechanisms. The results revealed that the mRNA and protein expression levels of Ep3 were significantly upregulated in NSCLC tissues and A549 cells. Pharmacological inhibition of Ep3 or RNA interference against Ep3 attenuated the cell viability, migration and invasion, and promoted apoptosis in A549 cells. Ep3 deficiency also decreased the expression of transforming growth factor (TGF)-β, phosphorylated (p)-Smad2 and p-Smad3. The transfection of TGF-β overexpression plasmids reversed the effects of Ep3 deficiency on the cell viability and apoptosis in A549 cells. Finally, an in vivo experiment revealed that Ep3-siRNA transfection strongly reduced the tumor growth and tumor volume. The Ep3-siRNA transfection also inhibited tumor metastasis via suppression of the expression of metastasis-associated proteins. Taken together, these findings indicate that inhibition of Ep3 attenuates the viability and migration, and promotes the apoptosis of NSCLC through suppression of the TGF-β/Smad signaling pathway. Targeting of the Ep3/TGF-β/Smad signaling pathway may be a novel therapeutic strategy for the prevention and treatment of NSCLC.