Cell Biology and Toxicology

, Volume 11, Issue 5, pp 273–281 | Cite as

Positive correlation between cellular glutathione and acquired cisplatin resistance in human ovarian cancer cells

  • G. Chen
  • K. -J. Hutter
  • W. J. Zeller
Article

Abstract

While multiple changes are frequently found to be associated with cisplatin resistance in a variety of tumor cell lines, a cause-effect relationship of these alterations with the resistant phenotype has not been established. In order to identify the resistance-relevant determinants, a series of cisplatinresistant sublines with different degrees of resistance to cisplatin was developed in a human ovarian carcinoma cell line (O-129). Three derived resistant cell lines displayed 2.1-fold (O-129/DDP4, low), 4.1-fold (O-129/DDP8, moderate) and 6.3-fold (O-129/DDP16, high) resistance, respectively, to cisplatin, compared with the sensitive parental line O-129. While the activity of poly(ADP-ribose) polymerase, an enzyme proposed to be involved in DNA repair, was elevated in all three resistant lines, a significant karyotypic change was observed only in the high-resistance line with the karyotype alteration from near diploidy to heteroploidy. The moderate (4.1-fold) and high (6.3-fold) DDP resistance was associated with a slow proliferation rate in drug-free medium, but cellular glutathione level was highly correlated with DDP sensitivity in all four cell lines. Taken together, the present studies establish that while many changes at cellular level can occur with development of cisplatin resistance, only elevation of intracellular glutathione concentration appears to be related to the resistance phenotype in these human ovarian cancer cells.

Key words

cisplatin resistance glutathione human ovarian cancer cells 

Abbreviations

DDP

cisplatin

FBS

fetal bovine serum

GSH

glutathione

IC50

drug concentration required to result in 50% growth inhibition

PARP

poly(ADP-ribose) polymerase

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Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • G. Chen
    • 1
  • K. -J. Hutter
    • 1
  • W. J. Zeller
    • 1
  1. 1.Forschungsschwerpunkt Diagnostik und Experimentelle TherapieDeutsches KrebsforschungszentrumHeidelbergGermany

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