22的绑定和调制estramustine耐多药表型。

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巴龙LR, Speicher LA,查普曼AE,住房和城市发展部GR,莱恩N,史密斯CD,东奔西走KD

22的绑定和调制estramustine耐多药表型。

中华肿瘤杂志,1994年5月4日,86 (9):688 - 94。

PubMed ID

7908988 (在PubMed

]

文摘

背景:先前的临床前研究的组合estramustine和长春花碱或紫杉醇(紫杉醇)已经表明,可以实现大于添加剂与这些antimicrotubule细胞毒性的药物组合。第二阶段研究hormone-refractory前列腺癌临床抗肿瘤活性充分展示了大小来刺激进一步的实验室和临床研究这些药物的组合。目的:我们的目的是描述的交互estramustine 22和确定它的影响。方法:标准的实验室技术被用来研究estramustine的影响细胞内的药物浓度,细胞毒性和诱导凋亡的信使核糖核酸(mRNA)(也称为PGY1)基因。使用光亲和模拟estramustine 17-0 - [[2 - (3 - (4-azido-3 - [125 i] -iodophenyl) propionamido)乙基]氨基甲酰)estradiol-3-N-bis (2-chloroethyl) ca rba伴侣([125 i] AIPP-estramustine)绑定到人类卵巢的膜蛋白(SKOV3)和他们的耐多药同行SKVLB1细胞进行了研究。印迹分析进行DNA提取人类前列腺癌野生型DU145 estramustine-resistant细胞系(E4)和SKVLB1细胞。结果:膜分数从SKOV3和SKVLB1细胞分析蛋白质可能与[125 i] AIPP-estramustine光亲和标记。竞争性抑制的绑定实现过剩浓度(的有效性)estramustine、长春花碱,维拉帕米,孕激素,在较小的程度上,通过与磷酸estramustine紫杉醇但不是,雌二醇、雌三醇。SKVLB1细胞积累较少[3 h]长春花碱和[3 h]紫杉醇比SKOV3细胞。Estramustine造成浓度增强药物积累SKVLB1细胞最多大约十二倍。 No effect of estramustine was apparent for the wild-type SKOV3 cells. In comparison with verapamil, estramustine was less effective as a modulator; however estramustine demonstrated good chemosensitizing activity in combination with actinomycin D and vinblastine. Neither short-term, low-dose no longer-term, higher concentration were found to produce measurable transcript (mRNA for the MDR1 gene levels. Such data suggest that, at least levels. Such data suggest that, at least for two distinct human cell line (SKOV3 and DU145), estramustine does not induce the overexpression of the MDR1 gene. CONCLUSION: It is apparent from the P-glycoprotein data that estramustine interacts with this efflux pump, altering intracellular drug accumulation. Overall, the nonempiric basis for including estramustine in clinical protocols that contain other multidrug-resistant drugs is strengthened by the present data.

DrugBank数据引用了这篇文章

药物转运蛋白

药物	转运体	类	生物	药理作用	行动
Estramustine	22 - 1	蛋白质	人类	未知的	抑制剂	细节