P-glycoprotein modulation improves in vitro chemosensitivity in malignant pediatric liver tumors.

BACKGROUND

Multidrug resistance (MDR) is a major reason for the poor outcome of advanced pediatric liver malignancies. The P-glycoprotein (P-gP), which contributes to this phenomenon, has been potently antagonized in other tumors. Our aim was to investigate the influence of P-gP antagonizers on the chemotherapy of pediatric liver malignancies in vitro.

MATERIALS AND

METHODS

One hepatocellular carcinoma (HCC) and three hepatoblastoma (HB) cell lines were incubated with doxorubicin or cisplatin. Additional effects of three P-gP-modulators were determined in a cytotoxicity assay. Expression levels of the MDR1 gene were determined using rT-PCR.

RESULTS

Modulation of P-gP improved chemotherapy results in all HB cell lines, more effectively in the more highly differentiated tumors. Combined treatment of the HCC cell line was only more efficient using doxorubicin and PSC 833.

CONCLUSION

Modulation of P-gP can overcome MDR in HCC and HB in vitro. Our data encourage further studies analyzing this effect under in vivo conditions.