International journal of cancer. Journal international du cancer
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We determined the effect of the highly selective cyclooxygenase-2 (COX-2) inhibitor NS-398 on proliferation, apoptosis and COX-2 regulation in 3 pre-malignant human colorectal adenoma cell lines (RG/C2, AA/C1, RR/C1) and compared its effect on 3 colorectal carcinoma cell lines (HT29, KS, JW2). COX-2 protein was expressed in each cell line derived from an adenoma, thus providing evidence that COX-2 is expressed in the tumour cells themselves at an early stage in human colorectal adenoma formation. NS-398 (20 to 100 microM for 96 h) induced apoptosis and inhibited the proliferation of the adenoma cell lines. ⋯ This was studied further in HT29 cultures, where treatment with NS-398 inhibited COX-2 activity, reducing prostaglandin E(2) secretion. Here, neither the increase in COX-2 protein expression nor the anti-proliferative and apoptosis-inducing effect of NS-398 was prevented by addition of exogenous prostaglandin E(2). Apoptosis appears to be the dominant anti-proliferative effect of NS-398 and, in COX-2 expressing cells, may be mechanistically linked to the observed induction of COX-2 protein expression upon treatment with NS-398.