多西紫杉醇
多重耐药
顺铂
癌症研究
癌细胞
米托蒽醌
生物
P-糖蛋白
化疗
癌症
医学
药理学
抗药性
内科学
微生物学
作者
Catherine Sánchez,Alejandro Mercado,Héctor R. Contreras,Patricia Mendoza,J. Cabezas,Cristián Acevedo,Christian Huidobro,Enrique A. Castellón
出处
期刊:The Prostate
[Wiley]
日期:2011-04-07
卷期号:71 (16): 1810-1817
被引量:32
摘要
Abstract BACKGROUND In several cancer types, expression of multidrug resistance (MDR) proteins has been associated with lack of chemotherapy response. In advanced prostate cancer (PCa) the use of chemotherapy is mainly palliative due to its high resistance. Previously, we described that MDR phenotype in PCa could be related with high basal and drug‐induced expression of MDR proteins P‐Glycoprotein (P‐Gp), MRP1, and LRP. METHODS Using primary cell cultures from PCa patients, we evaluated the effect of function and expression inhibition of P‐Gp, MRP1, and LRP, on cell survival after chemotherapy exposure. Cells were treated with specific MDR protein substrates (docetaxel and mitoxantrone for P‐Gp, methotrexate for MRP1 and cisplatin for LRP) and pharmacological inhibitors (cyclosporine A, genistein and 3‐aminobenzamide), and cell survival was evaluated trough 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) and cell cycle analysis. MRP1 activity was evaluated by FACS using the specific inhibitor MK571. Cells were transfected with MDR proteins siRNAs and treated with the corresponding substrates. RESULTS PCa cell resistance to MDR protein substrates was partially reversed, decreasing cell survival in around 20%, by treating primary cell cultures with specific pharmacological inhibitors. PCa cells transfected with siRNAs against MDR proteins decreased cell survival when treated with the corresponding drugs. Docetaxel was the most effective chemotherapeutic drug to induce cell death and decrease survival. CONCLUSION Low chemotherapy response in PCa could be explained, in part, by over‐expression of functional MDR proteins. Expression and function of these proteins should be evaluated to enhance efficacy of docetaxel‐based therapies of patients with hormone‐resistant PCa. Prostate 71:1810–1817, 2011. © 2011 Wiley Periodicals, Inc.
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