EGF通过STAT5调控肺腺癌A549细胞中COX-2的机制

BACKGROUND AND OBJECTIVE: It has been proved that cyclooxygenase-2 (COX-2) is a key factor in lung cancer oncogenesis.COX-2 can be induced by a number of cytokines and growth factors and can be regulated by the JAK/STAT signaling pathway.Inhibiting the expression of COX-2 can prevent the development of lung cancer.The aim fo this study is to investigate whether the epidermal growth factor (EGF) can stimulate the signal transducers and activators of transcription 5 (STAT5) as well as to discover the effects of the STAT5 signaling pathway on the COX-2 in human lung adenocarcinoma A549 cells. METHODS: The phenomenon of STAT5 activation stimulated by the EGF was assayed through immunofluorescence and Western blot.The adenovirus containing the wild-type (WT)-STAT5 (AdWT-STAT5) plasmid, dominant-negative (DN)-STAT5 (Ad-CMV5Stat5aΔ740) plasmid, and STAT5 siRNA were transfected into A549 cells.The latter two groups were stimulated using EGF. Reverse transcriptase polymerase chain reaction was used to detect the mRNA expression of COX-2. RESULTS: STAT5 was not activated in A549 cells in vitro.EGF stimulation significantly increased the level of the p-STAT5 protein and induces the shuttling of p-STAT5 from the cytoplasm into the nucleus.STAT5 activation was crucial for the COX-2 expression induced by the EGF.STAT5 was required for COX-2 expression, but can mediated the effects of the COX-2 expression through pathways that were independent of transcriptional activation. CONCLUSION: COX-2 expression is dependent on STAT5 phosphorylation.A second pathway does not require STAT5 phosphorylation.