Quercetin as a potential modulator of P-glycoprotein expression and function in cells of human pancreatic carcinoma line resistant to daunorubicin.
Quercetin as a potential modulator of P-glycoprotein expression and function in cells of human pancreatic carcinoma line resistant to daunorubicin.
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DOI：
10.3390/molecules15020857
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发表时间：
2010-02-09
期刊：
影响因子：
--
通讯作者：
Dziegiel P
中科院分区：
文献类型：
--
作者：
Borska S;Sopel M;Chmielewska M;Zabel M;Dziegiel P
P-糖蛋白（P-gp）是ABC转运蛋白之一，负责几种肿瘤对成功化疗的抗性。许多药剂能够干扰P-gp介导的药物输出，但不幸的是，它们中的大多数产生严重的副作用。一些植物多酚，包括黄酮醇槲皮素（Q），表现出抗肿瘤活性，主要是由于它们对细胞周期控制和细胞凋亡的影响。也有报道表明，Q可以增强细胞抑制药物的作用，抑制多药耐药（MDR）现象。该研究旨在确定Q是否通过其对P-gp表达和作用的影响而使对柔红霉素（DB）耐药的细胞增敏。实验在两种人胰腺癌细胞系上进行，作为对照，对DB EPP 85 - 181 RDB耐药和对EPP 85 - 181 P敏感。将两种细胞系的细胞暴露于选定浓度的Q和DB，然后检测P-gp的膜表达及其转运功能。并观察了对P-gp（ABCB 1）基因表达的影响。研究结果证实，Q以浓度依赖性方式影响P-gp的表达和功能。此外，它还降低了ABCB 1的表达。因此，Q可以被认为是P-gp的潜在调节剂。
P-glycoprotein (P-gp) is one of the ABC transporters responsible for the resistance of several tumours to successful chemotherapy. Numerous agents are capable of interfering with the P-gp-mediated export of drugs but unfortunately most of them produce serious side effects. Some plant polyphenols, including the flavonol quercetin (Q), manifest anti-neoplastic activity mainly due to their influence on cell cycle control and apoptosis. Reports are also available which show that Q may intensify action of cytostatic drugs and suppress the multidrug resistance (MDR) phenomenon. The study aimed at determination if Q sensitizes cells resistant to daunorubicin (DB) through its effect on P-gp expression and action. The experiments were conducted on two cell lines of human pancreatic carcinoma, resistant to DB EPP85-181RDB and sensitive EPP85-181P as a comparison. Cells of both lines were exposed to selected concentrations of Q and DB, and then membranous expression of P-gp and its transport function were examined. The influence on expression of gene for P-gp (ABCB1) was also investigated. Results of the studies confirmed that Q affects expression and function of P-gp in a concentration-dependent manner. Moreover it decreased expression of ABCB1. Thus, Q may be considered as a potential modulator of P-gp.
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影响因子：
5
作者：
Mitsunaga, Y;Takanaga, H;Sawada, Y
通讯作者：
Sawada, Y
影响因子：
7.2
作者：
Gupta, C.;Vikram, A.;Jena, G. B.
通讯作者：
Jena, G. B.
影响因子：
4.6
作者：
Hayeshi, Rose;Masimirembwa, Collen;Ungell, Anna-Lena B.
通讯作者：
Ungell, Anna-Lena B.
影响因子：
3.6
作者：
Kim, Y;Ma, AG;Suzuki, YJ
通讯作者：
Suzuki, YJ
影响因子：
64.8
作者：
LAEMMLI, UK
通讯作者：
LAEMMLI, UK