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Expression of multidrug resistance proteins in prostate cancer is related with cell sensitivity to chemotherapeutic drugs
The Prostate, 2009-09, Vol.69 (13), p.1448-1459
Sánchez, Catherine
Mendoza, Patricia
Contreras, Héctor R.
Vergara, Jorge
McCubrey, James A.
Huidobro, Christian
Castellón, Enrique A.
2009
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Sánchez, Catherine
Mendoza, Patricia
Contreras, Héctor R.
Vergara, Jorge
McCubrey, James A.
Huidobro, Christian
Castellón, Enrique A.
Titel
Expression of multidrug resistance proteins in prostate cancer is related with cell sensitivity to chemotherapeutic drugs
Ist Teil von
The Prostate, 2009-09, Vol.69 (13), p.1448-1459
Ort / Verlag
Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2009
Quelle
Wiley Online Library - AutoHoldings Journals
Beschreibungen/Notizen
BACKGROUND Multidrug resistance (MDR) proteins have been associated with the lack of chemotherapy response. Expression of these proteins has been described in the prostate, but there is no information about their role in the chemotherapy response of prostate cancer (PC). We studied the gene and protein expression of MDR proteins in primary cell cultures from PC tumors and PC cell lines, their relationship with chemotherapy and their effects on cell survival. METHODS Primary cell cultures from PC were obtained from samples provided by our Institutional Hospital. Cell lines LNCaP, PC3, and DU145 were also examined. Cells were treated during 72 hr with several chemotherapeutic drugs. Protein and mRNA expressions of P‐glycoprotein (P‐Gp), MRP1 and LRP, before and after drug treatment, were evaluated by RT‐PCR and Western blot analyses. The effect on cell survival was evaluated by proliferation assays (MTT), and cell cycle and apoptosis by flow cytometry. RESULTS Primary PC cultures exhibited higher MDR protein expression and lower drug sensitivity than cell lines, in which P‐Gp was not detected. Docetaxel and mitoxantrone displayed the highest apoptotic effect. Exposure to chemotherapeutic drugs increased apoptosis, cell cycle arrest, and MDR expression. Long‐term treatment with doxorubicin diminished apoptosis elicited by all drugs examined in this study, suggesting a cross‐resistance phenomenon. CONCLUSIONS Low chemotherapy response observed in PC primary cultures could be explained, in part, by the high levels of MDR proteins (intrinsic MDR phenotype), and also, by their over‐expression induced after long‐term exposure to drugs (acquired MDR phenotype), which increase treatment resistance. Prostate 69: 1448–1459, 2009. © 2009 Wiley‐Liss, Inc.
Sprache
Englisch
Identifikatoren
ISSN: 0270-4137
eISSN: 1097-0045
DOI: 10.1002/pros.20991
Titel-ID: cdi_proquest_miscellaneous_67624461
Format
–
Schlagworte
Antineoplastic Agents - pharmacology
,
apoptosis
,
Apoptosis - drug effects
,
ATP-Binding Cassette, Sub-Family B, Member 1 - genetics
,
Biological and medical sciences
,
Cell Survival - drug effects
,
chemotherapeutic drugs
,
Cisplatin - pharmacology
,
Drug Resistance, Neoplasm - genetics
,
Gynecology. Andrology. Obstetrics
,
Humans
,
Male
,
Male genital diseases
,
Medical sciences
,
Methotrexate - pharmacology
,
Mitoxantrone - pharmacology
,
multidrug resistance proteins
,
Multidrug Resistance-Associated Proteins - genetics
,
Nephrology. Urinary tract diseases
,
primary cell culture
,
prostate cancer
,
Prostatic Neoplasms - drug therapy
,
Prostatic Neoplasms - pathology
,
Prostatic Neoplasms - physiopathology
,
Taxoids - pharmacology
,
Tumor Cells, Cultured
,
Tumors
,
Tumors of the urinary system
,
Urinary tract. Prostate gland
,
Vault Ribonucleoprotein Particles - genetics
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