Exogenous expression of p21(WAF1/CIP1) exerts cell growth inhibition and enhances sensitivity to cisplatin in hepatoma cells.
The effects of exogenous expression of p21(WAF1/CIP1) in hepatoma cells were examined. Two stably p21(WAF1/CIP1)-transfected clones and one clone transfected with expression vector only were used for study. Introduction of p21(WAF1/CIP1) resulted in significant cell growth inhibition, and the magnitude of the cell growth inhibition in these transfected cells was proportional to the level of p21(WAF1/CIP1) protein expressed. Exogenous p21(WAF1/CIP1) expression also significantly enhanced chemosensitivity to cisplatin. In addition, apoptosis occurred earlier in cells transfected with p21(WAF1/CIP1) after cisplatin treatment. These findings raise the potential that forced upregulation of p21(WAF1/CIP1) in hepatocellular carcinoma (HCC) may reduce the doses of cisplatin to achieve similar responses and suggest the possible use of p21(WAF1/CIP1) in HCC treatment.
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Room 127B, University Pathology Building, Department of Pathology, the University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
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D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D002945:Cisplatin