Abstract 4673: The anti-proliferative effects of non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac and indomethacin in ovarian cancer cells

Abstract

Abstract Epidemiological studies have shown that the regular use of non-steroidal anti-inflammatory (NSAIDs) drugs is associated with a reduced risk of various cancers. In addition, in vitro and preclinical mouse model experiments have demonstrated that NSAIDs decrease tumor initiation and/or progression of several cancers. In an attempt to clarify the mechanisms of tumor prevention by NSAIDs, we have studied the effects of two NSAIDs, diclofenac and indomethacin, in several ovarian cancer cell lines. Diclofenac and indomethacin treatment decreased cell growth by inducing cell cycle arrest and/or apoptosis. To identify the possible molecular pathways mediating the effects of NSAID treatment in ovarian cancer, ovarian cancer cell lines were treated with diclofenac or indomethacin and microarray analysis was performed. Among the genes differentially expressed in the different cell lines were genes involved in signaling, metabolism, and cell cycle regulation. Some of the genes found downregulated following diclofenac or indomethacin treatment are transcriptional target genes of E2F1 and E2F4, suggesting involvement of these transcription factors in the response of ovarian cancer cells to NSAID treatment. In addition, E2F1 was found downregulated at the protein level upon treatment with diclofenac and indomethacin. The levels of phosphorylated Rb protein also decreased upon treatment with NSAIDs, suggesting activation of Rb and involvement of the Rb/E2F pathway in the effects of NSAID treatment in ovarian cancer cells. In conclusion, NSAIDs diclofenac and indomethacin exert an anti-proliferative effect in ovarian cancer cells and we have identified a number of target genes and pathways that may be important for the NSAID-induced cell cycle arrest and apoptosis. Current efforts are focused on determining the exact roles of these genes and pathways in NSAID-mediated cancer growth inhibition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4673. doi:1538-7445.AM2012-4673