Involvement of Multiple Cell Signaling Pathways in Cigarette Smoke induced Modulation of Ovarian Cancer Cell (OCC) Proliferation.

Abstract

Cigarette smoking is a known risk factor for many cancers but not the ovarian cancer. Our study examined whether cigarette smoke extract (CSE) affects ovarian cancer development using A2780 ovarian cancer cell (OCC) model. The major objective is to investigate the effects of CSE on OCC proliferation and unveil the responsible cell signaling mechanism. The specific aims are 1) to detect CSE induced OCC proliferation, 2) investigate estrogen's role and 3) unveil the responsible pathway.MethodsOCCs were cultured using standard methods. CSE was created according to a published protocol. OCCs were pre‐treated with several cell signaling pathway inhibitors and estrogen prior to CSE treatment. After CSE treatments (5%, 10% and 16%), WST‐1 reagent was added to each well, incubated for 3 hours, and the production of WST‐1 formazan, which is an indicative of cell proliferation, was detected.ResultsCSE stimulated OCC proliferation and this stimulation is significant in estrogen treated cells. Estrogen receptor / β2 adrenergic receptor blockage using the antagonist, ICI 118.551, has increased OCC proliferation and this increase was attenuated by CSE exposure. Blocking ERK1/2 pathway, using the antagonist U0126 significantly reduced CS induced OCC proliferation in non‐estrogen treated cells.ConclusionCSE activated OCC proliferation. Estrogen and β2 adrenergic receptor pathways showed protection towards OCC proliferation and CSE attenuated the protective effects. Activation of ERK signaling contributes to the CSE induced OCC proliferation in non – estrogen treated cells. In estrogen treated cells CS may cause OCC proliferation via non ERK related signaling.