Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 194-205 |
| Number of pages | 12 |
| Journal | Cancer Letters |
| Volume | 250 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jun 8 2007 |
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Keywords
- Cell cycle
- Cell viability
- Cisplatin
- Osteosarcoma cells
- Zoledronic acid
ASJC Scopus subject areas
- Cancer Research
- Molecular Biology
- Oncology
Cite this
Growth inhibition and sensitization to cisplatin by zoledronic acid in osteosarcoma cells. / Benassi, Maria Serena; Chiechi, Antonella; Ponticelli, Francesca; Pazzaglia, Laura; Gamberi, Gabriella; Zanella, Licciana; Manara, Maria Cristina; Perego, Paola; Ferrari, Stefano; Picci, Piero.
In: Cancer Letters, Vol. 250, No. 2, 08.06.2007, p. 194-205.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Growth inhibition and sensitization to cisplatin by zoledronic acid in osteosarcoma cells
AU - Benassi, Maria Serena
AU - Chiechi, Antonella
AU - Ponticelli, Francesca
AU - Pazzaglia, Laura
AU - Gamberi, Gabriella
AU - Zanella, Licciana
AU - Manara, Maria Cristina
AU - Perego, Paola
AU - Ferrari, Stefano
AU - Picci, Piero
PY - 2007/6/8
Y1 - 2007/6/8
N2 - 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.
AB - 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.
KW - Cell cycle
KW - Cell viability
KW - Cisplatin
KW - Osteosarcoma cells
KW - Zoledronic acid
UR - http://www.scopus.com/inward/record.url?scp=34047129164&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34047129164&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2006.10.004
DO - 10.1016/j.canlet.2006.10.004
M3 - Article
C2 - 17113707
AN - SCOPUS:34047129164
VL - 250
SP - 194
EP - 205
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 2
ER -