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Involvement of Multiple Cell Signaling Pathways in Cigarette Smoke induced Modulation of Ovarian Cancer Cell (OCC) Proliferation.
Author(s) -
Sumanasekera Wasana,
Ngo Dung,
Tran Liem,
Nguyen Tanya,
Castle Marilin
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.974.20
Subject(s) - cell growth , estrogen , cancer research , mapk/erk pathway , estrogen receptor , signal transduction , ovarian cancer , medicine , pharmacology , endocrinology , chemistry , cancer , biology , microbiology and biotechnology , breast cancer , biochemistry
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. Methods OCCs 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. Results CSE 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. Conclusion CSE 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.