Abstract
Mutant p53-carrying tumors are often more resistant to chemotherapeutical drugs. We demonstrate here that the mutant p53-reactivating compound PRIMA-1MET acts synergistically with several chemotherapeutic drugs to inhibit tumor cell growth. Combined treatment with cisplatin and PRIMA-1MET resulted in a synergistic induction of tumor cell apoptosis and inhibition of human tumor xenograft growth in vivo in SCID mice. The induction of mutant p53 levels by chemotherapeutic drugs is likely to increase the sensitivity of tumor cells to PRIMA-1MET. Thus, the combination of PRIMA-1MET with currently used chemotherapeutic drugs may represent a novel and more efficient therapeutic strategy for treatment of mutant p53-carrying tumors.
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Acknowledgements
This work was supported by the Swedish Cancer Society (Cancerfonden), Cancerföreningen, Karolinska Institute, the Ingabritt & Arne Lundberg Foundation and EC FP5 and FP6 Funding. The information in this document is provided as is and no guarantee or warranty is given that the information is fit for any particular purpose. The user thereof uses the information at its sole risk and liability. The Community is not liable for any use that may be made of the information contained herein. We thank Bert Vogelstein, Johns Hopkins Oncology Center, for HCT116 cells, Peter Chumakov, Engelhard Institute of Molecular Biology, Moscow, for H1299-His175 cells and Farzan Rastinejad, Pfizer Central Research, for CP31398.
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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc)
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Bykov, V., Zache, N., Stridh, H. et al. PRIMA-1MET synergizes with cisplatin to induce tumor cell apoptosis. Oncogene 24, 3484–3491 (2005). https://doi.org/10.1038/sj.onc.1208419
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DOI: https://doi.org/10.1038/sj.onc.1208419
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