Nuclear medicine and biology, 2013-05, Vol.40 (4), p.471-480
2013
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- Autor(en) / Beteiligte
- Titel
- Apoptosis and p53 are not involved in the anti-tumor efficacy of 125I-labeled monoclonal antibodies targeting the cell membrane
- Ist Teil von
- Nuclear medicine and biology, 2013-05, Vol.40 (4), p.471-480
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 125I-labeled monoclonal antibodies (125I-mAbs) can efficiently treat small solid tumors. Here, we investigated the role of apoptosis, autophagy and mitotic catastrophe in 125I-mAb toxicity in p53−/− and p53+/+ cancer cells. We exposed p53−/− and p53+/+ HCT116 cells to increasing activities of internalizing (cytoplasmic location) anti-HER1 125I-mAbs, or non-internalizing (cell surface location) anti-CEA 125I-mAbs. For each targeting model we established the relationship between survival and mean nucleus absorbed dose using the MIRD formalism. In both p53−/− and p53+/+ HCT116 cells, anti-CEA 125I-mAbs were more cytotoxic per Gy than anti-HER1 125I-mAbs. Sensitivity to anti-CEA 125I-mAbs was p53-independent, while sensitivity to anti-HER1 125I-mAbs was higher in p53−/− HCT 116 cells, suggesting that they act through different signaling pathways. Apoptosis was only induced in p53+/+ HCT116 cells and could not explain cell membrane radiation sensitivity. Inhibition of autophagy did not modify the cell response to 125I-mAbs. By contrast, mitotic death was similarly induced in both p53−/− and p53+/+ HCT116 cells by the two types of 125I-mAbs. We also showed using medium transfer experiments that γ-H2AX foci were produced in bystander cells. Cell membrane sensitivity to 125I-mAbs is not mediated by apoptosis and is p53-independent. Bystander effects-mediated mitotic death could be involved in the efficacy of 125I-mAbs binding cell surface receptors.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0969-8051eISSN: 1872-9614DOI: 10.1016/j.nucmedbio.2013.02.001Titel-ID: cdi_proquest_miscellaneous_1399913327
- Format
- –
- Schlagworte
- 125I-mAbs, Antibodies, Monoclonal - metabolism, Antibodies, Monoclonal - pharmacology, Antibodies, Monoclonal - therapeutic use, Antineoplastic Agents - metabolism, Antineoplastic Agents - pharmacology, Antineoplastic Agents - therapeutic use, Apoptosis, Apoptosis - drug effects, Apoptosis - radiation effects, Auger electrons, Bystander Effect - radiation effects, Cell Membrane - drug effects, Cell Membrane - metabolism, Cell Membrane - radiation effects, Cytoplasm - drug effects, Cytoplasm - metabolism, Cytoplasm - radiation effects, HCT116 Cells, Humans, Iodine Radioisotopes - therapeutic use, Mitosis - drug effects, Mitosis - radiation effects, Molecular Targeted Therapy, p53, Protein Transport - radiation effects, Radioimmunotherapy, Receptor, Epidermal Growth Factor - metabolism, Tumor Suppressor Protein p53 - metabolism