TY - JOUR
T1 - Induction of resistance to Aplidin® in a human ovarian cancer cell line related to MDR expression
AU - Tognon, Gianluca
AU - Bernasconi, Sergio
AU - Celli, Nicola
AU - Faircloth, Glynn T.
AU - Cuevas, Carmen
AU - Jimeno, José
AU - Erba, Eugenio
AU - D'Incalci, Maurizio
PY - 2005/12
Y1 - 2005/12
N2 - 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.
AB - 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.
KW - Aplidin®
KW - Flow cytometry
KW - Marine natural compound
KW - Pgp expression
KW - Resistant cell line
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M3 - Article
C2 - 16258264
AN - SCOPUS:31144462030
SN - 1538-4047
VL - 4
SP - 1325
EP - 1330
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
IS - 12
ER -