Antiproliferative Effect Of Cyclooxygenase-2 Gene Silencing On Human Hepatoma Cells And The Underlying Mechanism

Objective: Cyclooxygenase-2(COX-2) is one of the key enzymes in conversion of arachidonic acid to prostaglandins. It is undetectable in most normal tissues, but is rapidly induced by both mitogenic and inflammatory stimuli such as cytokines, growth factors, oncogenes and tumor promoters, resulting in enhanced synthesis of prostanoids in neoplastic and inflamed tissues. Aberrant COX-2 expression has been observed in over 80% of human colorectal adenocarcinomas and some cancers of other organ sites, including lungs, stomach, esophagus, cervix, skin, bladder, pancreas and head and neck. Data from epidemiological, genetic and pharmacological studies demonstrate multiple roles of COX-2 in carcinogenesis including inhibition of apoptosis, immune suppression and promotion of angiogenesis and tumor invasion.Roles of COX-2 in hepatocarcinogenesis remain to be determined. COX-2 up-regulation has been found in chronic hepatitis, cirrhosis and well-differentiated HCC, but less so in poorly differentiated hepatocellular carcinoma (HCC), suggesting that COX-2 is involved in early step of hepatocarcinogenesis. However, decreased COX-2 expression in less-differentiated HCC implies that COX-2 might exert a negative effect on tumor progression. COX-2 inhibitors have been reported to supress HCC growth in animal models and cultured cells, but the COX-2-independent mechanism is suggested for the growth inhibition, for the reason that proliferation of COX-2 non-expressed cells has also been inhibited by those COX-2 inhibitors.