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.
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.
Authors: Steven W Warmann; Sorin Armeanu; Heike Heitmann; Peter Ruck; Guido Seitz; Johannes T Wessels; Marie-Luise Lemken; Ulrich M Lauer; Jörg Fuchs; Michael Bitzer Journal: Pediatr Surg Int Date: 2006-07-29 Impact factor: 1.827
Authors: Guido Seitz; Steven W Warmann; Christian O Vokuhl; Heike Heitmann; Claudia Treuner; Ivo Leuschner; Jörg Fuchs Journal: Pediatr Surg Int Date: 2007-05 Impact factor: 2.003
Authors: C Eicher; A Dewerth; J Thomale; V Ellerkamp; S Hildenbrand; S W Warmann; J Fuchs; S Armeanu-Ebinger Journal: Br J Cancer Date: 2012-12-20 Impact factor: 7.640