Transcriptional analysis of doxorubicin-induced cytotoxicity and resistance in human hepatocellular carcinoma cell lines.

Background/aims: Hepatoma is either intrinsically resistant to chemotherapy or response to it but later develop resistance. The aim of this study was to clarify the relationship of treatment with doxorubicin (Dox) in hepatoma HepG2 cells and drug resistance developed by Dox.

Methods: We have analysed the bioactivities and gene expression profiles of multidrug resistant (MDR) HepG2/DR cell line and its parental HepG2 cell, which were exposure to Dox.

Results: We confirmed that Dox-induced apoptosis of HepG2 cells in a time-dependent manner; cDNA microarray and hierarchical cluster analysis demonstrate that the features of the transcriptional programme of the later response to Dox in HepG2 cells and MDR HepG2/DR cells have a common character, which is upregulation of stress response, cytoskeleton, ubiquitin-proteasome pathway and repressed G-protein signal transduction system; differentially expressed genes in MDR HepG2/DR such as drug transporters and tumour-associated antigens were verified at the levels of mRNA by semiquantitative reverse transcriptase-polymerase chain reaction.

Conclusions: These results reveal novel co-ordinated changes that occurred in resistant HepG2 cells to survive from cell apoptosis elicited by Dox treatment.