Cox-2 unabhängige Zielgene selektiver NSAIDs in kolorektalen Karzinomzellen

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are able to inhibit the growth of colorectal cancer cells. This effect could be shown in cyclooxygenase-2⁺ (COX-2⁺) as well as in COX-2^- cell lines. Therefore other effects than the known COX-2 inhibition must be also responsible for the tumoricidal activity of NSAIDs. To evaluate the involvement of COX-2-independent mechanisms we assessed the effects of Nabumetone and Celecoxib on cell survival, cell cycle and apoptosis in a COX-2⁺ (HT29) and a COX-2^- (DLD1) colorectal carcinoma cell line. Both drugs induced in both cell lines a G1 arrest. The cell death was detectable in both cell lines after Celecoxib but not after Nabumetone treatment. Increased expression of 5 genes on mRNA level was detectable in a cDNA array in both cell lines after treatment. The following genes were upregulated more than two-fold after treatment: GADD153, MIC1/NAG1, VEGF, DTR, PC4 homolog. This data indicate that several genes potentially involved in induction of cell arrest and/or apoptosis are activated by NSAIDs in a COX-2-independent manner. This may explain tumoricidal effects of NSAIDs in COX-2^-cell lines.