Acquired anticancer drug resistance in
cancer cells is often a result of an increase in levels of the
ATP binding cassette (
ABC) transporters that export anticancer drugs from
cancer cells, suggesting that anticancer drugs may induce genes that mediate drug resistance in
cancer cells. In this study, the induction of anticancer drug transporter gene expression by
Adriamycin was examined in human
lung cancer cell lines. Increased expression of MDR1, MRP5 and SMRP
mRNA was observed 48 hr after the initiation of
Adriamycin exposure in human
lung cancer PC-14 cells and
cisplatin-resistant PC-14/CDDP cells, in a dose-dependent manner as measured by TaqMan real-time RT-PCR. The levels of
MRP-1, MRP2 and LRP
mRNA were not altered by
Adriamycin exposure. The biologic functions of the MRP5 and SMRP genes have not been fully clarified. To elucidate the relationship between
Adriamycin resistance and MRP5 and SMRP,
mRNA levels of MRP5 and SMRP in
Adriamycin-resistant cell lines were compared with the parental cells. Increased expression of MRP5 and SMRP
mRNA was observed in all 3 cell lines (SBC-3/ADM, AdR MCF7 and K562/ADM) by Northern blot analysis and
RNase protection assay. These results suggest that subacute exposure of
lung cancer cells to
Adriamycin induced MRP5 and SMRP and that long-term exposure with
Adriamycin selected the MRP5- and SMRP-overexpressing
lung cancer cells. MRP5 and SMRP is a candidate molecule for acquired
Adriamycin resistance in addition to MDR1.