MEGESTROL-ACETATE REVERSES MULTIDRUG RESISTANCE AND INTERACTS WITH P-GLYCOPROTEIN
MEGESTROL-ACETATE REVERSES MULTIDRUG RESISTANCE AND INTERACTS WITH P-GLYCOPROTEIN
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DOI：
10.1007/bf00684845
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发表时间：
1992-04-01
影响因子：
3
通讯作者：
SAFA, AR
中科院分区：
文献类型：
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作者：
FLEMING, GF;AMATO, JM;SAFA, AR
我们评估了黄体酮（PRG）和一种口服活性的结构相关化合物醋酸甲孕酮（MA）在几种耐多药人类细胞系中的多药耐药（MDR）调节作用。在100 μ m时，这两种类固醇都抑制了MDR人神经母细胞SH-SY5Y/VCR细胞中长春花生物碱光亲和类似物与p -糖蛋白（P-gp）的结合[在四氮唑染料（MTT）试验中，长春新碱（VCR）的抗性达到1500倍]。然而，在SH-SY5Y/VCR细胞和MDR人表皮样KB-GSV2细胞系中，100 μ m MA显著增强了[H-3]-azidopine与P-gp的结合（MTT试验显示其对VCR的抗性为250倍）。PRG对[H-3]-叠氮多啶与P-gp的结合影响不大。低剂量MA比PRG更能使细胞对VCR增敏并促进[H-3]-VCR的积累。高度耐药的SH-SY5Y/VCR亚系对这两种类固醇均表现出显著的侧枝敏感性。这些数据表明，MA可能是临床有用的MDR调节剂。
We evaluated the multidrug resistance (MDR)-modulating effects of progesterone (PRG) and an orally active, structurally related compound, megestrol acetate (MA), in several MDR human cell lines. At 100-mu-M, both steroids inhibited the binding of a Vinca alkaloid photoaffinity analog to P-glycoprotein (P-gp) in MDR human neuroblastic SH-SY5Y/VCR cells [which show > 1500-fold resistance to vincristine (VCR) in the tetrazolium dye (MTT) assay]. However, 100-mu-M MA markedly enhanced the binding of [H-3]-azidopine to P-gp in both SH-SY5Y/VCR cells and the MDR human epidermoid KB-GSV2 cell line (which displays 250-fold resistance to VCR in the MTT assay). PRG had little effect on the binding of [H-3]-azidopine to P-gp. MA at low doses was more effective than PRG in sensitizing cells to VCR and enhancing their accumulation of [H-3]-VCR. The highly resistant SH-SY5Y/VCR subline exhibited significant collateral sensitivity to both steroids. These data suggest that MA may be a clinically useful modulator of MDR.