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Metallothionein gene expression and resistance to cisplatin in human ovarian cancer

โœ Scribed by R. J. Schilder; L. Hall; A. Monks; L. M. Handel; A. J. Fornace Jr.; R. F. Ozols; A. T. Fojo; T. C. Hamilton

Publisher
John Wiley and Sons
Year
1990
Tongue
French
Weight
792 KB
Volume
45
Category
Article
ISSN
0020-7136

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โœฆ Synopsis

lntracellular thiols have been proposed as mediators of resistance to alkylating agents and cisplatin. As metallothionein is the predominant protein thiol, we examined its relationship to cisplatin resistance in human ovarian cancer cell lines. A human ovarian carcinoma cell line, A2780, derived from an untreated patient, was treated with cisplatin in several ways and the induced resistance to cisplatin ranged from 13to 68-fold. The degree of resistance was dependent upon the method of selection. The drug-resistant cell lines also developed low levels of cross-resistance to cadmium. Additional cell lines established from untreated patients or ovarian can- cer patients refractory t o cisplatin-and/or carboplatincontaining combination chemotherapy were studied. The most cisplatin-resistant cell lines, OVCAR-8 and -10, were from patients previously treated with intensive chemotherapy. OVCAR-8 was relatively cross-resistant to cadmium while OVCAR-10 appeared relatively sensitive. Cell lines were examined for expression of metallothionein mRNA to evaluate the relationship between cisplatin resistance, cadmium cross-resistance and metallothionein expression. Only

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