Isolation and characterization of an IGROV-1 human ovarian cancer cell line made resistant to Ecteinascidin-743 (ET-743)

E. Erba, D. Bergamaschi, L. Bassano, S. Ronzoni, G. Di Liberti, I. Muradore, S. Vignati, G. Faircloth, J. Jimeno, M. D'Incalci

Research output: Contribution to journalArticle

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Abstract

By exposing Igrov-1 human ovarian cancer cells to increasing concentrations of Ecteinascidin-743 (ET-743), either for a short or prolonged time. we obtained sublines resistant to ET-743 which overexpress Pgp. The most resistant clone (Igrov-1/25 ET) was evaluated for biological and pharmacological characterizations. The increased Pgp levels of Igrov-1/25 ET were not due to amplification of the mdr-1 gene but to increased mRNA levels. No increase in other multidrug resistance-related proteins such as MRP or LRP was observed in Igrov-1/25 ET. The IC50 values of ET-743 against Igrov-1/25 ET was approximately 50 times higher than the parental cell line. Resistance was not reversed while maintaining the cell line in drug-free medium for at least 24 months. Igrov-1/25 ET was cross-resistant to Doxorubicin and VP16 while it was equally sensitive to L-PAM, MNNG, CPT and only marginally less sensitive to Cis-DDP and Oxaliplatin compared to the parental cell line. Igrov-1/25 ET exposed to Doxorubicin retained this drug much less, mainly because of a more efficient drug efflux. The cyclosporine analogue SDZ PSC-833 reversed the resistance of Igrov-1/25 ET to ET-743, without any enhancement of the drug activity against the parental Igrov-1 cell line. Igrov-1/25 ET exhibits typical features of cell lines overexpressing the mdr-l gene and can be a potentially useful tool in selecting ET-743 non-cross-resistant analogues as well as to investigate methods to counteract resistance to this drug. (C) 2000 Cancer Research Campaign.

Original languageEnglish
Pages (from-to)1732-1739
Number of pages8
JournalBritish Journal of Cancer
Volume82
Issue number10
Publication statusPublished - 2000

Fingerprint

trabectedin
Ovarian Neoplasms
Cell Line
oxaliplatin
Pharmaceutical Preparations
Doxorubicin
P-Glycoproteins
Methylnitronitrosoguanidine
Melphalan
Drug Resistance
Cyclosporine
Genes
Inhibitory Concentration 50
Clone Cells
Pharmacology
Messenger RNA

Keywords

  • Drug-resistance
  • Ecteinascidin-743
  • Natural compound
  • P-gp expression

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Erba, E., Bergamaschi, D., Bassano, L., Ronzoni, S., Di Liberti, G., Muradore, I., ... D'Incalci, M. (2000). Isolation and characterization of an IGROV-1 human ovarian cancer cell line made resistant to Ecteinascidin-743 (ET-743). British Journal of Cancer, 82(10), 1732-1739.

Isolation and characterization of an IGROV-1 human ovarian cancer cell line made resistant to Ecteinascidin-743 (ET-743). / Erba, E.; Bergamaschi, D.; Bassano, L.; Ronzoni, S.; Di Liberti, G.; Muradore, I.; Vignati, S.; Faircloth, G.; Jimeno, J.; D'Incalci, M.

In: British Journal of Cancer, Vol. 82, No. 10, 2000, p. 1732-1739.

Research output: Contribution to journalArticle

Erba, E, Bergamaschi, D, Bassano, L, Ronzoni, S, Di Liberti, G, Muradore, I, Vignati, S, Faircloth, G, Jimeno, J & D'Incalci, M 2000, 'Isolation and characterization of an IGROV-1 human ovarian cancer cell line made resistant to Ecteinascidin-743 (ET-743)', British Journal of Cancer, vol. 82, no. 10, pp. 1732-1739.
Erba E, Bergamaschi D, Bassano L, Ronzoni S, Di Liberti G, Muradore I et al. Isolation and characterization of an IGROV-1 human ovarian cancer cell line made resistant to Ecteinascidin-743 (ET-743). British Journal of Cancer. 2000;82(10):1732-1739.
Erba, E. ; Bergamaschi, D. ; Bassano, L. ; Ronzoni, S. ; Di Liberti, G. ; Muradore, I. ; Vignati, S. ; Faircloth, G. ; Jimeno, J. ; D'Incalci, M. / Isolation and characterization of an IGROV-1 human ovarian cancer cell line made resistant to Ecteinascidin-743 (ET-743). In: British Journal of Cancer. 2000 ; Vol. 82, No. 10. pp. 1732-1739.
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abstract = "By exposing Igrov-1 human ovarian cancer cells to increasing concentrations of Ecteinascidin-743 (ET-743), either for a short or prolonged time. we obtained sublines resistant to ET-743 which overexpress Pgp. The most resistant clone (Igrov-1/25 ET) was evaluated for biological and pharmacological characterizations. The increased Pgp levels of Igrov-1/25 ET were not due to amplification of the mdr-1 gene but to increased mRNA levels. No increase in other multidrug resistance-related proteins such as MRP or LRP was observed in Igrov-1/25 ET. The IC50 values of ET-743 against Igrov-1/25 ET was approximately 50 times higher than the parental cell line. Resistance was not reversed while maintaining the cell line in drug-free medium for at least 24 months. Igrov-1/25 ET was cross-resistant to Doxorubicin and VP16 while it was equally sensitive to L-PAM, MNNG, CPT and only marginally less sensitive to Cis-DDP and Oxaliplatin compared to the parental cell line. Igrov-1/25 ET exposed to Doxorubicin retained this drug much less, mainly because of a more efficient drug efflux. The cyclosporine analogue SDZ PSC-833 reversed the resistance of Igrov-1/25 ET to ET-743, without any enhancement of the drug activity against the parental Igrov-1 cell line. Igrov-1/25 ET exhibits typical features of cell lines overexpressing the mdr-l gene and can be a potentially useful tool in selecting ET-743 non-cross-resistant analogues as well as to investigate methods to counteract resistance to this drug. (C) 2000 Cancer Research Campaign.",
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