title: Aspirin Blocks EGF-stimulated Cell Viability in a COX-1 Dependent Manner in Ovarian Cancer Cells.
abstract: OBJECTIVE
  Although aspirin has been associated with a reduction of the risk of cancer when used as a nonsteroidal anti-inflammatory drug, its use to reduce the risk of ovarian cancer is controversial. Ovarian cancer cells usually express high levels of cyclooxygenase-1 (COX)-1. Because aspirin is a rather selective inhibitor of COX-1, the ability of aspirin to reduce the risk of ovarian cancer may be dependent on the level of COX-1 expression in those cells. Furthermore, epidermal growth factor receptor (EGFR) is frequently overexpressed in the malignant phenotype of ovarian cancer leading to increased cell proliferation and survival. Here we investigated if aspirin attenuates EGFR-activated ovarian cancer cell growth in a COX-1 dependent manner.
  
  
  METHODS
  Cell viability assays and Western blot analyses were used to determine the effect of aspirin on EGF-stimulated cell proliferation. Gene silencing and gene expression techniques were employed to knockdown or to express COX-1, respectively.
  
  
  RESULTS
  Aspirin inhibited cell viability induced by EGF in a dose dependent manner in COX-1 positive ovarian cancer cells. On the other hand, aspirin had no effect on cell viability in COX-1 negative ovarian cancer cells. In particular, aspirin decreased phosphorylated Akt and Erk activated by EGF. COX-1 silencing in COX-1 positive cells attenuated the inhibitory effect of aspirin on EGF-stimulated cell viability. Furthermore, we developed a COX-1 expressing cell line (SKCOX-1) by stably transfecting COX-1 expression vector into COX-1 negative SKOV-3 cells. SKCOX-1 cells were more responsive to aspirin when compared to cells transfected with empty vector, and decreased EGF-activated Akt and Erk as well as cell viability.
  
  
  CONCLUSIONS
  Taken together, aspirin inhibits viability of ovarian cancer cells by blocking phosphorylation of Akt and Erk activated by EGF. Thus it may potentiate the therapeutic efficacy of drugs used to treat COX-1 positive ovarian cancer subsets.
authors.affiliation: 1. Department of Internal Medicine, Barnes-Jewish hospital, Saint Louis, MO 63110, USA.
authors.forename: May
authors.initials: M
authors.lastname: Cho
authors.forename: Syeda M
authors.initials: SM
authors.lastname: Kabir
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Dong
authors.forename: Eunsook
authors.initials: E
authors.lastname: Lee
authors.forename: Valerie Montgomery
authors.initials: VM
authors.lastname: Rice
authors.forename: Dineo
authors.initials: D
authors.lastname: Khabele
authors.forename: Deok-Soo
authors.initials: DS
authors.lastname: Son
keywords: Akt; COX-1; EGF; Erk; aspirin; cell viability.; ovarian cancer