二氢吡啶衍生物对依托泊苷耐药的人前列腺癌细胞系中非P-糖蛋白介导的多药耐药性的逆转作用。
Reversal by a dihydropyridine derivative of non-P-glycoprotein-mediated multidrug resistance in etoposide-resistant human prostatic cancer cell line.
作者信息
Tasaki Y, Nakagawa M, Ogata J, Kiue A, Tanimura H, Kuwano M, Nomura Y
机构信息
Department of Urology and Surgery, Oita Medical University, Japan.
出版信息
J Urol. 1995 Sep;154(3):1210-6.
PURPOSE
We have isolated etoposide-resistant prostatic cancer cell lines, P/VP10 and P/VP20, to investigate the multidrug resistance (MDR) mechanism and to find MDR reversal agents.
MATERIALS AND METHODS
We examined expression of MDR-related genes and screened reversal agents of MDR in P/VP20 cells.
RESULTS
These cells demonstrated a non-P-glycoprotein (P-gp)-mediated MDR phenotype with overexpression of MDR-associated protein (MRP) mRNA due to MRP DNA amplification. A 1,4-dihydropyridine derivative, bis(4-pyridylmethyl)4-[2-(3-methyl-5,6- dihydro-1,4-dithiinyl)]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicar boxylate (NIK250), was found to overcome MDR in P/VP20 cells.
CONCLUSIONS
NIK250 might be useful in reversing MDR, which often develops during chemotherapy of advanced or hormone-resistant prostatic cancer.
目的
我们分离出了依托泊苷耐药的前列腺癌细胞系P/VP10和P/VP20，以研究多药耐药（MDR）机制并寻找MDR逆转剂。
材料与方法
我们检测了P/VP20细胞中MDR相关基因的表达并筛选了MDR逆转剂。
结果
这些细胞表现出非P-糖蛋白（P-gp）介导的MDR表型，由于MRP DNA扩增，MDR相关蛋白（MRP）mRNA过表达。发现一种1,4-二氢吡啶衍生物双（4-吡啶甲基）4-[2-（3-甲基-5,6-二氢-1,4-二硫杂环戊烯基）]-2,6-二甲基-1,4-二氢吡啶-3,5-二羧酸酯（NIK250）可克服P/VP20细胞中的MDR。
结论
NIK250可能有助于逆转晚期或激素抵抗性前列腺癌化疗期间经常出现的MDR。
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