In several neoplastic diseases, including hepatocellular carcinoma, the expression of P-glycoprotein and cyclooxygenase-2 (COX-2) are often increased and involved in drug resistance and poor prognosis.
Conversely, it was observed that apoptosis induced by the alpha-linolenic acid-enriched diet correlated with a decrease in arachidonate content in hepatoma cells and decreased cyclooxygenase-2 expression.
Increased expression of cyclooxygenase-2 protein during rat hepatocarcinogenesis caused by a choline-deficient, L-amino acid-defined diet and chemopreventive efficacy of a specific inhibitor, nimesulide.
In vitro studies have revealed that both NS-398, a selective COX-2 inhibitor, and sulindac, an analog of nonsteroidal anti-inflammatory drugs, effectively inhibit growth of human hepatoma cell lines, which is mediated by a decreased rate of cell proliferation.