Multidrug resistance in androgen-independent growing rat prostate carcinoma cells is mediated by P-glycoprotein
| Autor: | Peter Alken, Annette Steidler, T. Nebe, K. U. Köhrmann, C. Kreukler, M. Siegsmund |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Male
Antimetabolites Antineoplastic Neoplasms Hormone-Dependent Paclitaxel Urology Antineoplastic Agents Drug resistance Vinblastine Tumor Cells Cultured medicine Animals Cytotoxic T cell Rhodamine 123 ATP Binding Cassette Transporter Subfamily B Member 1 Etoposide Fluorescent Dyes P-glycoprotein Cisplatin Antibiotics Antineoplastic biology Rhodamines Prostatic Neoplasms Antineoplastic Agents Phytogenic Molecular biology Drug Resistance Multiple Rats Multiple drug resistance Methotrexate Verapamil Doxorubicin Drug Resistance Neoplasm Cell culture Androgens biology.protein Efflux Genes MDR medicine.drug |
| Zdroj: | Urological Research. 25:35-42 |
| ISSN: | 1434-0879 0300-5623 |
| DOI: | 10.1007/bf00941904 |
| Popis: | Prostate carcinomas are in general resistant against virtually all cytotoxic drugs. Up to now it has not been thoroughly evaluated whether specific resistance factors, such as the expression of the MDR1 gene, play a role in this multi-agent resistance and whether there is a link between drug resistance and hormone-independent growth. We investigated the resistance patterns of a hormone-sensitive and four hormone-independent Dunning rat carcinoma sublines against four drugs which are substrates of P-glycoprotein (vinblastine, taxol, doxorubicin, and etoposide) and two agents (methotrexate and cis-platinum) which are not transported by this efflux pump. All hormone-insensitive sublines, AT.1, AT. 3.1., MatLu and Mat LyLu, continuously showed a clearly enhanced resistance (3- to 26-fold) against the P-glycoprotein substrates, compared to the hormone-sensitive subline G. Only two of the androgen-independent sublines displayed enhanced resistance against methotrexate, whereas all of them were more sensitive against cisplatin than the androgen-sensitive G cells. By addition of verapamil the resistance against vinblastine (9- to 10-fold) and taxol (6.7- to 26.7-fold) in the hormone-insensitive cells could be almost totally reversed. Furthermore, the fluorescent P-glycoprotein substrate rhodamine-123 was effectively pumped out of the four tested hormone-independent cell lines, whereas the hormone-sensitive G cells were unable to extrude the dye. By reverse transcriptase polymerase chain reaction (RT-PCR) with primers specific for the rat mdr1b gene, the homologue to the human MDR1 gene, we could easily detect mdr1b expression in the androgen independent cell lines, but not in the G cells. Our results suggest that the product of the rat mdr1b gene is involved in the multidrug resistance of androgen-independent Dunning prostate carcinoma cells. |
| Databáze: | OpenAIRE |
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