Adriamycin accumulation and metabolism in adriamycin-sensitive and -resistant human ovarian cancer cell lines. 1986

K G Louie, and T C Hamilton, and M A Winker, and B C Behrens, and T Tsuruo, and R W Klecker, and W M McKoy, and K R Grotzinger, and C E Myers, and R C Young

Adriamycin accumulation and metabolism were studied in three distinct groups of human ovarian cancer cell lines: those derived from previously untreated patients, those from clinically refractory (relapsed) patients, and those with induced resistance to adriamycin in vitro. The 2-hr [14C] adriamycin accumulation in cell lines from previously untreated patients (A2780 and A1847 [Eva et al., Nature, Lond. 295, 116 (1982)] and OVCAR-5 [National Institutes of Health human OVarian CAR-cinoma cell line no. 5]) was 11-14 ng/10(6) cells. 2780AD and 1847AD (variants with in vitro induced resistance to adriamycin) accumulated one-third as much adriamycin after 2 hr (4 ng/10(6) cells). However, three cell lines derived from clinically refractory patients accumulated the same amount of adriamycin as cell lines from untreated patients (8-13 ng/10(6) cells). A high-performance liquid chromatography (HPLC) assay for adriamycin and its analogs confirmed these results and demonstrated only parent drug (no metabolites) in any of the cell lines tested. These results demonstrate that the primary mechanism of adriamycin resistance in some ovarian cancer cells from clinically refractory patients is not enhanced metabolism of drug or a transport defect leading to a decreased net accumulation such as has been described for cells with in vitro induced resistance to adriamycin.

UI MeSH Term Description Entries
D010051 Ovarian Neoplasms Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS. Cancer of Ovary,Ovarian Cancer,Cancer of the Ovary,Neoplasms, Ovarian,Ovary Cancer,Ovary Neoplasms,Cancer, Ovarian,Cancer, Ovary,Cancers, Ovarian,Cancers, Ovary,Neoplasm, Ovarian,Neoplasm, Ovary,Neoplasms, Ovary,Ovarian Cancers,Ovarian Neoplasm,Ovary Cancers,Ovary Neoplasm
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004317 Doxorubicin Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN. Adriamycin,Adriablastin,Adriablastine,Adriblastin,Adriblastina,Adriblastine,Adrimedac,DOXO-cell,Doxolem,Doxorubicin Hexal,Doxorubicin Hydrochloride,Doxorubicin NC,Doxorubicina Ferrer Farm,Doxorubicina Funk,Doxorubicina Tedec,Doxorubicine Baxter,Doxotec,Farmiblastina,Myocet,Onkodox,Ribodoxo,Rubex,Urokit Doxo-cell,DOXO cell,Hydrochloride, Doxorubicin,Urokit Doxo cell
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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