COX-2 - a target for preventing hepatic carcinoma?
Hepatocellular carcinoma (HCC) is one of the most common reasons for malignancy-related death in Africa and Asia and is still recognised as the leading cancer in men in Taiwan. Despite enthusiastic efforts in early diagnosis, aggressive surgical treatment and application of additional nonoperative modalities, its prognosis is still dismal. This emphasises the necessity to develop new measures and strategies for its prevention. Inducible cyclooxygenease 2 (COX-2) is an immediate-early (IE) response gene and extensive studies conducted over the past few years have recognised its overexpression in several carcinomas and thus its implication in carcinogenesis. Recent studies have suggested that overexpression of COX-2 might be one of the leading factors in hepatic carcinogenesis. COX-2 can induce angiogenesis via vascular endothelial growth factor (VEGF) and prostaglandin production and can also inhibit apoptosis by inducing the antiapoptotic factor Bcl-2 as well as activating antiapoptotic signalling through Akt/PKB. Therefore, the use of selective inhibitors for the downregulation of COX-2 activity might be a target for preventing hepatic carcinoma development.
Rahman
Mohammad A
MA
Second Department of Surgery, Shimane Medical University, Izumo 693-8501, Japan. rahman@shimane-med.ac.jp
Kohno
Hitoshi
H
Nagasue
Naofumi
N
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000502:physiology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D018450:Disease Progression; D004354:Drug Screening Assays, Antitumor; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control*; D008565:Membrane Proteins / Q000502:physiology; D009363:Neoplasm Proteins / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human