Sign up for Table of Contents Alerts.
Email this page
Print this page
Research Paper
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 and Maurizio D’Incalci
volume 4 | issue 12
december 2005Pages: 1325-1330
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.
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 8 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: (i) increased expression of membrane-associated P-glycoprotein, (ii) 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 overexpressing 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.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.