Induction of resistance to Aplidin® in a human ovarian cancer cell line related to MDR expression

Gianluca Tognon, Sergio Bernasconi, Nicola Celli, Glynn T. Faircloth, Carmen Cuevas, José Jimeno, Eugenio Erba, Maurizio D'Incalci

Research output: Contribution to journalArticle

Abstract

Aplidin®-resistant IGROV-1/APL cells were derived from the human ovarian cancer IGROV-1 cell line by exposing the cells to increasing concentration of Aplidin® for eight months, starting from a concentration of 10 nM to a final concentration of 4 μM. IGROV-1/APL cell line possesses five fold relative resistance to Aplidin®. IGROV-1/APL resistant cell line shows the typical MDR phenotype: (1) increased expression of membrane-associated P-glycoprotein, (2) cross-resistance to drugs like etoposide, doxorubicin, vinblastine, vincristine, taxol, colchicin and the novel anticancer drug Yondelis™ (ET-743). The Pgp inhibitor cyclosporin-A restored the sensitivity of IGROV-1/APL cells to Aplidin® by increasing the drug intracellular concentration. The resistance to Aplidin® was not due to the other proteins, such as LPR-1 and MRP-1, being expressed at the same level in resistant and parental cell line. The finding that cells over-expressing Pgp are resistant to Aplidin® was confirmed in CEM/VLB 100 cells, that was found to be 5-fold resistant to Aplidin® compared to the CEM parental cell line.

Original languageEnglish
Pages (from-to)1325-1330
Number of pages6
JournalCancer Biology and Therapy
Volume4
Issue number12
Publication statusPublished - Dec 2005

Keywords

  • Aplidin®
  • Flow cytometry
  • Marine natural compound
  • Pgp expression
  • Resistant cell line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Tognon, G., Bernasconi, S., Celli, N., Faircloth, G. T., Cuevas, C., Jimeno, J., Erba, E., & D'Incalci, M. (2005). Induction of resistance to Aplidin® in a human ovarian cancer cell line related to MDR expression. Cancer Biology and Therapy, 4(12), 1325-1330.