Saupe Madeleine, Rauschenberger Lisa, Preuß Melanie, Oswald Stefan, Fussek Sebastian, Zimmermann Uwe, Walther Reinhard, Knabbe Cornelius, Burchardt Martin, Stope Matthias B
Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.
Department of Pharmacology, Center of Drug Absorption and Transport (C_DAT), University Medicine Greifswald, Felix-Hausdorf-Straße 3, 17487, Greifswald, Germany.
World J Urol. 2015 Oct;33(10):1481-6. doi: 10.1007/s00345-014-1469-0. Epub 2014 Dec 28.
The development of a drug-resistant phenotype is the major challenge during treatment of castration-resistant prostate cancer (PC). In solid cancer entities, one of the major contributors to chemoresistance is the multidrug resistance 1 (MDR1) protein. Believed to be involved in the induction of MDR1 expression is the presence of anticancer drugs as well as the Y box binding protein 1 (YB-1).
Basal as well as drug-induced expression of MDR1 in established PC cell lines was assessed by Western blotting and mass spectrometry. Subsequently, the influence of YB-1 on MDR1 expression was examined via transient overexpression of YB-1.
While LNCaP and PC-3 cells showed no detectable amounts of MDR1, the resistance factor was found to be expressed in 22Rv1 cells. Despite this difference, all three cell lines demonstrated similar growth behavior in the presence of the first-line chemotherapeutic agent docetaxel. Incubation of 22Rv1 cells with docetaxel, cabazitaxel, and abiraterone did not significantly alter MDR1 expression levels. Furthermore, overexpression of the MDR1 controlling factor YB-1 showed no impact on MDR1 expression levels.
MDR1 was detectable in the PC cell line 22Rv1. However, this study suggests that MDR1 is of less importance for drug resistance in PC cells than in other types of solid cancer. Furthermore, in contrast to YB-1 properties in other malignancies, MDR1 regulation through YB-1 seems to be unlikely.
耐药表型的形成是去势抵抗性前列腺癌（PC）治疗过程中的主要挑战。在实体癌中，多药耐药1（MDR1）蛋白是导致化疗耐药的主要因素之一。抗癌药物以及Y盒结合蛋白1（YB-1）被认为与MDR1表达的诱导有关。
通过蛋白质印迹法和质谱法评估已建立的PC细胞系中MDR1的基础表达以及药物诱导表达。随后，通过YB-1的瞬时过表达来检测YB-1对MDR1表达的影响。
虽然LNCaP和PC-3细胞未检测到MDR1，但在22Rv1细胞中发现了耐药因子的表达。尽管存在这种差异，但在一线化疗药物多西他赛存在的情况下，所有三种细胞系均表现出相似的生长行为。用多西他赛、卡巴他赛和阿比特龙孵育22Rv1细胞并未显著改变MDR1的表达水平。此外，MDR1控制因子YB-1的过表达对MDR1的表达水平没有影响。
在PC细胞系22Rv1中可检测到MDR1。然而，本研究表明，与其他类型的实体癌相比，MDR1在PC细胞耐药中所起的作用较小。此外，与YB-1在其他恶性肿瘤中的特性相反，通过YB-1调节MDR1似乎不太可能。
