Document Detail

Growth inhibition and sensitization to cisplatin by zoledronic acid in osteosarcoma cells.
MedLine Citation:
PMID:  17113707     Owner:  NLM     Status:  MEDLINE    
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.
Maria Serena Benassi; Antonella Chiechi; Francesca Ponticelli; Laura Pazzaglia; Gabriella Gamberi; Licciana Zanella; Maria Cristina Manara; Paola Perego; Stefano Ferrari; Piero Picci
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-11-20
Journal Detail:
Title:  Cancer letters     Volume:  250     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-04-11     Completed Date:  2007-06-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  194-205     Citation Subset:  IM    
Laboratory of Oncologic Research, Rizzoli Orthopaedic Institute, Bologna, Italy.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Blotting, Western
Cell Cycle / drug effects
Cell Division / drug effects*
Cell Line, Tumor
Cisplatin / pharmacology*
Diphosphonates / pharmacology*
Drug Screening Assays, Antitumor
Imidazoles / pharmacology*
Osteosarcoma / metabolism,  pathology*
RNA, Small Interfering
Retinoblastoma Protein / metabolism
Tumor Suppressor Protein p53 / metabolism
Reg. No./Substance:
0/Antineoplastic Agents; 0/Diphosphonates; 0/Imidazoles; 0/RNA, Small Interfering; 0/Retinoblastoma Protein; 0/Tumor Suppressor Protein p53; 118072-93-8/zoledronic acid; 15663-27-1/Cisplatin

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