There is compelling evidence for the reduction of the incidense and severity of cancers associated with the use of non steroidal anti-inflammatory drugs. We investigated the cellular and gene expression pattern changes following the in vitro application of two NSAIDs, diclofenac and indomethacin on several ovarian cancer cell lines and in vivo after administration in a xenograph model. We saw a reduction in the number of viable cells due to an increase in apoptosis and cell cycle arrest. After illumina microarray analysis, E2F1 was found to be a target. Since ovarian cancer cells over express claudins-3 and -4, we decided to investigate the possibility of using CPE, an enterotoxin known to function via these two tight junction proteins, as a potential therapeutic. In vitro assays were set up utilizing several ovca cell lines with varying claudin expression patturns. While indeed cells that expressed claudin-3 and -4 did experience a market reduction in viability, it was discovered that those cells that expressed caludin 6 were also targeted. This represented a novel receptor for the enterotoxin. Speroids created with claudin-6 expressing cells, also confirmed this novel finding.
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