Expression of Bcl-2 family proteins during chemotherapeutic agents-induced apoptosis in the hepatoblastoma HepG2 cell line.
This study demonstrates that two anticancer drugs, taxol and doxorubicin (Dox), can kill human hepatoblastoma HepG2 cells in a dose-dependent manner via the induction of apoptosis. Characteristic events, including externalization of phosphatidylserine, cytoplasmic shrinkage, chromatin condensation and DNA degradation, were observed in a large majority of the drug-treated cells. DNA fragmentation showed that a ladder of DNA fragments of approximately 200 bp multiples was observed in taxol-treated, but not in Dox-treated, cells. In addition, the expression patterns of Bcl-2 family members during taxol or Dox treatment were investigated. Results from Western blot analysis indicated that HepG2 cells did not express either the death repressor Bcl-2, or the death promoters Bcl-XS and Bax. However, during the apoptotic process one death repressor, Bcl-XL, and two death promoters, Bak and Bad, were expressed. The expression levels of Bcl-XL and Bak remained unchanged, whereas the level of Bad was down-regulated. As the ratio between death repressors and death promoters in the Bcl-2 family will determine the sensitivity of cells to apoptotic stimuli, the findings suggest that the changed expression patterns of Bcl-2 family proteins caused by anticancer drugs in liver cancer cells may be involved in chemoresistance.
Luo
D
D
Department of Biology, Hong Kong University of Science and Technology, SAR, China.
Cheng
S C
SC
Xie
Y
Y
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018197:Hepatoblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2