Induction of apoptosis by cisplatin and its effect on cell cycle-related proteins and cell cycle changes in hepatoma cells.
We investigated cisplatin-induced apoptosis and the effects on cell cycle-related proteins and cell cycle changes. Two human hepatoma cell lines, HepG2 (with wild-type p53) and Hep3B (with deleted p53), were treated with different concentrations of cisplatin. Cisplatin induced apoptosis in both cell lines as assessed by cell morphology, DNA fragmentation analysis,TdT-mediated dUTP nick end labeling assay and flow cytometry. HepG2 cells were more sensitive to cisplatin than Hep3B. Low-dose cisplatin induced a transient G(1) arrest, S phase block and upregulation of p53 and p21(WAF1/CIP1) expression in HepG2, but not in Hep3B cells. With cisplatin at a high dose, both cell lines underwent apoptosis that was accompanied by downregulation of p27(KIP1) and Bcl-x(L). In HepG2, upregulation of p53 and p21(WAF1/CIP1) was observed before apoptosis occurred, suggesting that cisplatin-induced apoptosis in HepG2 might be p53-dependent. Expression of Fas was also increased following cisplatin treatment in HepG2. However, there was no induction of p53, p21(WAF1/CIP1) and Fas observed in Hep3B cells. In conclusion, cisplatin induced apoptosis in hepatoma cells via both p53-dependent and -independent pathways.
Qin
Lan F
LF
Department of Pathology and Centre for the Study of Liver Disease, The University of Hong Kong, Room 127B, University Pathology Building, Queen Mary Hospital, Pokfulam, Hong Kong.
Ng
Irene O L
IO
D000199:Actins / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002945:Cisplatin / Q000633:toxicity*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007700:Kinetics; D008113:Liver Neoplasms / Q000473:pathology*; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics
D000199:Actins; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019014:fas Receptor; D002945:Cisplatin