BH3-mimetic drugs prevent tumour onset in an orthotopic mouse model of hepatoblastoma
| Autor: | Julia Wenz, Jörg Fuchs, Sorin Armeanu-Ebinger, Justus Lieber, Verena Ellerkamp, Fabian Vogt, Steven W. Warmann |
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| Rok vydání: | 2013 |
| Předmět: |
Hepatoblastoma
Indoles Cell Drug Evaluation Preclinical Mice Nude Mice Transgenic Biology Piperazines Metastasis Nitrophenols chemistry.chemical_compound Mice Immune system Immunity Biomimetic Materials Mice Inbred NOD Proto-Oncogene Proteins medicine Animals Humans Pyrroles Cells Cultured Sulfonamides Biphenyl Compounds Liver Neoplasms Cell migration Cell Biology medicine.disease Peptide Fragments Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Cell Transformation Neoplastic chemistry Apoptosis Immunology Cancer research Obatoclax |
| Zdroj: | Experimental cell research. 322(1) |
| ISSN: | 1090-2422 |
| Popis: | Drug resistance and metastasis remain major challenges in the treatment of high-risk hepatoblastoma (HB) and require the development of alternative therapeutic strategies. Modulation of apoptosis in HB cells enhances the sensitivity of these cells towards various drugs and has been discussed to enforce treatment. We investigated the impact of apoptosis sensitisers, BH3-mimetics, on the interaction between the host and HB to reduce tumour growth and dissemination while enhancing immunity. BH3-mimetics, such as obatoclax and ABT-737, enhanced the apoptosis-inducing effect of TRAIL and TNF-α resistant HB cells (HepT1 and HUH6). Tumour cell migration was inhibited by ABT-737 and more markedly by obatoclax. In an orthotopic model of HB, tumour uptake was reduced when the cells were pretreated with low concentrations of obatoclax. Only 1 of 7 mice developed HB in the liver, compared with an incidence of 0.8 in the control group. In summary, our study showed that apoptosis sensitisers had broader effects on HB cells than expected including migration and susceptibility to cytokines in addition to the known effects on drug sensitization. Sensitising HB to apoptosis may also allow resistant HB to be targeted by immune cells and prevent tumour cell dissemination. |
| Databáze: | OpenAIRE |
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