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

P. Perego, S. C. Righetti, R. Supino, D. Delia, C. Caserini, N. Carenini, B. Bedogné, E. Broome, S. Krajewski, J. C. Reed, F. Zunino

Research output: Contribution to journalArticle

Abstract

Since apoptosis is the primary mode of cell death induced by cisplatin, the role of apoptosis and 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-OS/Pt) and in ovarian carcinoma (A2780/CP) cells with wild-type p53, bcl-2 levels were markedly reduced. U2-OS/Pt cells had a 16-fold increase in the level of Bcl-xL protein. Stable transfection of U2-OS cells with bcl-xL cDNA conferred a low level of drug resistance to 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.

Original languageEnglish
Pages (from-to)540-548
Number of pages9
JournalApoptosis
Volume2
Issue number6
Publication statusPublished - 1997

    Fingerprint

Keywords

  • Apoptosis
  • bcl-2
  • Cisplatin resistance
  • p53

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

Perego, P., Righetti, S. C., Supino, R., Delia, D., Caserini, C., Carenini, N., Bedogné, B., Broome, E., Krajewski, S., Reed, J. C., & Zunino, F. (1997). Role of apoptosis and apoptosis-related proteins in the cisplatin-resistant phenotype of human tumor cell lines. Apoptosis, 2(6), 540-548.