Abstract:
Doxorubicin is one of the most potent anticancer drugs used in the treatment of various cancer
types. The efficacy of doxorubicin is influenced by the drug resistance mechanisms
and its cytotoxicity. In this study, we performed a high-copy screening analysis to find genes
that play a role in doxorubicin resistance and found several genes (CUE5, AKL1, CAN1,
YHR177W and PDR5) that provide resistance. Among these genes, overexpression of
PDR5 provided a remarkable resistance, and deletion of it significantly rendered the tolerance
level for the drug. Q-PCR analyses suggested that transcriptional regulation of these
genes was not dependent on doxorubicin treatment. Additionally, we profiled the global
expression pattern of cells in response to doxorubicin treatment and highlighted the genes
and pathways that are important in doxorubicin tolerance/toxicity. Our results suggest that
many efflux pumps and DNA metabolism genes are upregulated by the drug and required
for doxorubicin tolerance.
