Overcoming cisplatin resistance through p53 gene using caffeine in osteosarcoma

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1) Alteration of p53 gene in human osteosarcoma cell lines : There was no overexpression of p53 gene and no point mutation from exon 5 to exon 8 in both OST cell line (sensitive to cisplatin) and OST-R cell line (resistant to cisplatin). It was considered that these two cell lines expressed wild-type p53 protein.2) Analysis of p53 deletion in cisplatin-resistant human osteosarcoma cell (OST-R) : Deletion of p53 gene was significantly increased in OST-R cells. As the amount of p53 protein was decreased corresponding with this deletion, the function of p53 was suppressed and the instability of chromosome 17 was increased in OST-R.Perhaps, the function loss of p53 gene and protein would be an indicator of acquired cisplatin resistance in human osteosarcoma.3) Alteration of p53 gene expression after chemotherapy and growth inhibition by controlling p53 expression : Caffeine has DNA-repair inhibiting effect and suppress p53 overexpression. The cytocidal effect of cisplatin was increased by caffeine in OST cells, but not in OST-R.The expression of p53 protein was overexpressed after cisplatin treatment and caffeine suppressed this overexpression in OST cells. Caffeine could not overcome the acquired cisplatin-resistance in human osteosarcoma.