Cyclooxygenase-2 (COX-2) is directly involved but not decisive in proliferation of human hepatocellular carcinoma cells |
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Authors: | Joong-Won Park Jung Eun Park Jung Ahn Lee Chang-Woo Lee Chang-Min Kim |
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Affiliation: | (1) Research Institute, National Cancer Center, Goyang, Korea;(2) Center for Liver Cancer, National Cancer Center, 809 Madu 1-dong, Ilsan-gu, 411-769 Goyang, Gyeonggi, South Korea |
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Abstract: | Expression of cyclooxygenase-2 (COX-2) is involved in the chronic inflammation-related development of hepatocellular carcinoma
(HCC), and the use of selective COX-2 inhibitors might provide new chemoprevention strategies for HCC. However, the role of
the COX-2 in hepatocarcinogenesis remains obscure, particularly as it has been primarily studied with selective COX-2 inhibitors
that may affect other cellular proteins involved in cell proliferation. Therefore, we investigated the effects of the inhibition
of COX-2 by the selective COX-2 inhibitor NS-398 as well as by COX-2 specific small interfering RNA (siRNA) in the human HCC
cell lines Hep3B and SNU-387. These cell lines expressed COX-2, and NS-398 induced apoptosis of these cells. NS-398 inhibited
more than 60% of prostaglandin E2 (PGE2) production and cell proliferation in a concentration-dependent manner in these cells. The inhibition of proliferation
was almost restored with PGE2 supplement, suggesting that NS-398 may inhibit cell growth partially through inhibition of COX-2
and PGE2 production in human HCC cells. However, treatment with NS-398 led to increased expression of COX-2 in Hep3B and SNU-387
cells. To examine the effect of COX-2 depletion on these cells, we electroporated COX-2-specific siRNAs into SNU-387 cells.
We observed significant, sequence-specific reductions in COX-2 expression, PGE2 production, and cell proliferation, though
the reduction in cell proliferation was less than that induced by NS-398. In conclusion, these data suggest that COX-2 itself
is directly involved, though not decisively, in proliferation of human HCC cells. RNA interference may provide a useful tool
for manipulating COX-2-related hepatocarcinogenesis in research and therapeutic settings.
Supported by National Cancer Center, Korea grant 02101203 |
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Keywords: | Cyclooxygenase-2 Hepatocellular carcinoma siRNA Growth inhibition |
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