Role of apoptosis and apoptosis-related proteins in the cisplatin-resistant phenotype of human tumor cell lines

Since apoptosis is the primary made of cell death induced by cisplatin, the role of apoptosis acid apoptosis-related gene products in cisplatin resistance was Investigated in four human cisplatin-resistant cell lines of different tumour type. A common feature of the resistant sublines was a reduced susceptibility to drug-induced apoptosis compared to parental sensitive lines. Loss of wild-type p53 function was not a general event associated with the development of drug resistance. an increased bcl-2 expression was found in resistant cells characterized by mutant p53 (A431/Pt and IGROV-1?/Pt), whereas in osteosarcoma (U2-PS/Pt) and in ovarian carcinoma (A2780/CP) cells with wildtype p53, bcl-2 levels were markedly reduced. U2-OS/Pt cells had a 16-fold increase In the level of Bcl-x(L) protein, Stable transfection of CIP-CIS cells with bcl-x(L) cDNA conferred a low Level of drug resistance io cisplatin, suggesting that overexpression of this gene contributes to the cisplatin-resistant phenotype of this osteosarcoma cell system. in conclusion, these observations suggest a variable contribution of apoptosis-related genes to cisplatin resistance depending on the biological background of the cell system and presumably reflecting different pathways of apoptosis.