Induction of Apoptosis and Inhibition of Cell Growth in Human Hepatocellular Carcinoma Cells by COX‐2 Inhibitors

• DOI: 10.1196/annals.1322.052
• Publication Date: 2005-01-13T20:08:46Z
• Authors: DANIELA FODERÀ; NATALE D'ALESSANDRO; ANTONELLA CUSIMANO; PAOLA POMA; MONICA NOTARBARTOLO; NADIA LAMPIASI; GIUSEPPE MONTALTO; MELCHIORRE CERVELLO
• Keywords: Carcinoma, Hepatocellular; Time Factors; Cyclooxygenase 2 Inhibitors; Dose-Response Relationship, Drug; Neovascularization, Pathologic; Reverse Transcriptase Polymerase Chain Reaction; Anti-Inflammatory Agents, Non-Steroidal; Cell Cycle; Membrane Proteins; antineoplastic activity, apoptosis, cancer cell culture,; Apoptosis; Flow Cytometry; Inhibitory Concentration 50; 03 medical and health sciences; 0302 clinical medicine; Cyclooxygenase 2; Prostaglandin-Endoperoxide Synthases; Cell Line, Tumor; Humans; Protein Isoforms; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Cell Proliferation

Abstract: The aim of the present study was to examine the effects of nonselective (indomethacin) and selective cyclooxygenase‐2 (COX‐2) inhibitors (NS‐398, nimesulide, and CAY10404) on cell growth, cell cycle distribution, and apoptosis in three human hepatocellular carcinoma cell lines (HepG2, HuH‐6, and HA22T/VGH) with different characteristics of differentiation and biological behavior. The four COX inhibitors showed a dose‐dependent growth‐inhibitory effect in all the cell lines. No substantial arrests in the progression of the cells through the cell cycle were observed after treatment of HuH‐6 or HA22T/VGH for 48 h with the various inhibitors. On the other hand, there were significant increases in apoptosis, with the highest effect of cell kill being seen after treatment with indomethacin, especially in HuH‐6. Our findings support the suggestion that selective or, perhaps more efficiently, nonselective COX‐2 inhibitors may have potential therapeutic effects in hepatocellular carcinoma. Further studies must be carried out to better determine the possible mechanisms of these effects.