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

Tognon, Gianluca,1976Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin,Institute of Internal Medicine (författare)

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 microM. 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.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmakologi och toxikologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmacology and Toxicology hsv//eng
Antibiotics
Antineoplastic
pharmacology
Antineoplastic Agents
pharmacology
Antineoplastic Agents
Alkylating
pharmacology
Antineoplastic Agents
Phytogenic
pharmacology
Cell Line
Tumor
Cyclosporine
pharmacology
Depsipeptides
pharmacology
Dose-Response Relationship
Drug
Drug Resistance
Multiple
Drug Resistance
Neoplasm
Enzyme Inhibitors
pharmacology
Female
Genes
MDR
Humans
Isoquinolines
pharmacology
Ovarian Neoplasms
metabolism
pathology
P-Glycoprotein
metabolism
Peptides
Cyclic
pharmacology

Av författaren/redakt...: Tognon, Gianluca ...; Bernasconi, Serg ...; Celli, Nicola; Faircloth, Glynn ...; Cuevas, Carmen; Jimeno, José; visa fler...; Erba, Eugenio; D'Incalci, Mauri ...; visa färre...

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