Secretory phospholipase A2 mediates human esophageal adenocarcinoma cell growth and proliferation via ERK 1/2 pathway.

Background/aim: Secretory phospholipase-A2 (sPLA2) mediates growth and proliferation of human esophageal adenocarcinoma cells (HEAC). Two major molecular pathways of cancer growth regulation include extracellular signal-regulated kinase 1/2 (ERK 1/2) and protein kinase-B (AKT). Phospholipase enzymes have been demonstrated to significantly influence these two growth regulating pathways in other tumor cells. We hypothesize sPLA2 to mediate HEAC growth control through ERK 1/2 and AKT.

Materials And Methods: Verified HEAC (FLO-1), treated with either the mitogen-activated protein kinase kinase selective inhibitor (PD98059) or with group IIa sPLA2-specific inhibitor, were assessed for ERK1/2 phosphorylation and AKT activation after tumor necrosis factor-alpha stimulation, as well as for viability, proliferation, and apoptosis responses.

Results: PD98059 significantly inhibited ERK 1/2 activation, reduced cell viability, and reduced proliferation (p<0.05). sPLA2 inhibition attenuated ERK 1/2 activation (p<0.01) but had no effect on AKT activation or apoptosis.

Conclusion: Specific inhibition of group IIa sPLA2 directly reduces HEAC viability and proliferation by attenuating ERK 1/2 activation with no effect on AKT activation or apoptosis. This may indicate that the mechanism of action of sPLA2 is mainly the induction of growth arrest.