Growth inhibition and sensitization to cisplatin by zoledronic acid in osteosarcoma cells
| Autor: | Licciana Zanella, Paola Perego, Francesca Ponticelli, Laura Pazzaglia, Maria Cristina Manara, Antonella Chiechi, Stefano Ferrari, Gabriella Gamberi, Piero Picci, Maria Serena Benassi |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Cell cycle checkpoint Blotting Western Cell Antineoplastic Agents Retinoblastoma Protein Zoledronic Acid chemistry.chemical_compound Cell Line Tumor medicine Humans RNA Small Interfering Cisplatin Osteosarcoma Diphosphonates Chemistry Cell Cycle Imidazoles Cell cycle medicine.disease Zoledronic acid medicine.anatomical_structure Oncology Biochemistry Cell culture Cancer research Drug Screening Assays Antitumor Tumor Suppressor Protein p53 Growth inhibition Cell Division medicine.drug |
| Zdroj: | Cancer Letters. 250:194-205 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2006.10.004 |
| Popis: | Since osteosarcoma is a drug-resistant disease, the aim of the present study was to explore the possible interest of therapeutic approaches including nitrogen-containing biphosphonate zoledronic acid using osteosarcoma cell lines with different genetic backgrounds. Parental p53+/pRb+ U2-OS, p53-mutant U2-OS (U2-OS/175) and p53-/pRb- SAOS were sensitive to zoledronic acid with no significant differences in IC50 values. Analysis of cell cycle distribution revealed a time-dependent shifting of U2-OS cells towards G2 phase with cell cycle arrest in G2 phase at 96 h of exposure to the compound. Conversely, U2-OS/175 and SAOS cells responded to treatment with transient cell accumulation in S phase up to 48-72 h, respectively. Cell lines were exposed to increasing concentrations of cisplatin alone or combined with sub-toxic doses of zoledronic acid. A growth inhibitory effect was seen after combined treatment in U2-OS, otherwise resistant to cisplatin up to 100 ng/ml. Zoledronic acid did not efficiently sensitized U2-OS/175 and SAOS to cisplatin, thereby suggesting that different behavior may depend on p53 mutation. This data was confirmed in U2-OS cells where p53 expression was downregulated by RNA interference. Present findings indicate occurrence of sensitization to cisplatin by zoledronic acid in wild-type p53 osteosarcoma cells but not in p53-null cells nor in cells expressing a dominant-negative form of p53, supporting that wild-type p53 is required for synergistic interaction of cisplatin and zoledronic acid. |
| Databáze: | OpenAIRE |
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