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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

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

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