Epidermal growth factor stimulates the proliferation of human esophageal squamous cell carcinoma HKESC-1 cells by increasing COX-2 expression / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the mechanisms responsible for epidermal growth factor (EGF)-induced proliferation of human esophageal squamous cell carcinoma cells.</p><p><b>METHODS</b>(3)H-thymidine incorporation assay was used to assess the proliferation of HKESC-1 cells exposed to EGF stimulation. Enzyme immunoassay was used to measure PGE(2) release from HKESC-1 cells, and the protein levels of cyclooxygenase 1 (COX-1), COX-2, EP1 and EP2 in EGF-stimulated cells were determined by Western blotting.</p><p><b>RESULTS</b>EGF upregulated COX-2 protein expression but produced no obvious effect on COX-1 protein expression in HKESC-1 cells. As a consequence of increased COX-2, EGF further enhanced cellular PGE(2) release. EGF stimulation also resulted in increased protein expression of EP2, a subtype of PGE(2) receptors. Both the non-selective COX inhibitor indomethacin and the selective COX-2 inhibitor SC-236 completely abolished EGF-induced PGE(2) release, and suppressed the mitogenic effect of EGF.</p><p><b>CONCLUSION</b>EGF stimulates the proliferation of HKESC-1 cells by increasing COX-2 protein expression and PGE(2) release. Upregulated EP2 protein expression may further amplify the mitogenic action of PGE(2).</p>