Overexpression of multidrug resistance genes MDR1 and cMOAT in human hepatocellular carcinoma and hepatoblastoma cell lines.

Overexpression of either of the multidrug resistance genes MDR1 and MRP is associated with resistance of tumors to multiple chemotherapeutic agents. Overexpression of MDR1 has been reported in some cell lines derived from human hepatocellular carcinomas (HCC) and hepatoblastomas (HB). The human gene for cMOAT (<canalicular multispecific organic anion transporter>), a homologue of MRP, is thought to mediate hepatobiliary excretion of organic anions and to be associated with cisplatin resistance. In this study, expression levels of MDR1 and cMOAT were examined in 9 human HCC and HB cell lines and 10 other human cancer cell lines. Overexpression of the cMOAT gene was observed in all 9 HCC and HB cell lines and 3 of 10 other cancer cell lines. Co-overexpression of the cMOAT and MDR1 genes was observed in 7 of 9 HCC and HB cell lines, but in none of the 10 other cancer cell lines. Seven of the HCC and HB cell lines that had overexpression of the cMOAT gene were shown to be highly resistant to cisplatin compared to 2 HCC cell lines with low levels of cMOAT expression. These findings suggest that overexpression of cMOAT could contribute to cisplatin resistance in HCC and HB.