R-dl-verapamil downmodulates multidrug resistance of KBv200 cells to vincristine and doxorubicin.

Zhongguo yao li xue bao = Acta pharmacologica Sinica Pub Date : 1999-07-01

G Fang, Y L Yang, J S Li, Z X Zhang

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Abstract

Aim: To study the attenuation of multidrug resistance (MDR) by R-dl-verapamil (R-Ver) and the acute animal toxicity of R-Ver, and to compare these results of R-Ver with the results of dl-verapamil (Ver).

Methods: Cytotoxicity was determined by tetrazolium (MTT) assay. Cellular accumulation of doxorubicin (Dox) was measured by fluorescence spectrophotometry. Acute animal toxicity was tested by i.p. drug administration in BALB/c mice.

Results: R-Ver attenuated MDR of KBv200 cells to vincristine (VCR) and Dox. This attenuation ability was dose-related, and was also dependent on drug exposure time. R-Ver 1.25 mumol.L-1 increased the sensitivity of KBv200 cells to VCR (P < 0.01) with a 24-h period of drug exposure. R-Ver downmodulated MDR and increased cellular Dox accumulation of KBv200 cells as effectively as Ver, but possessed lower acute toxicity in BALB/c mice. While LD50 of Ver was 60 (49-73) mg.kg-1, LD50 of R-Ver was 166 (137-202) mg.kg-1.

Conclusion: R-Ver downmodulated the MDR to VCR and Dox at 1.25 mumol.L-1, and this effect on VCR can be realized with drug exposure duration of 24 h.

本刊更多论文

r -dl-维拉帕米下调KBv200细胞对长春新碱和阿霉素的多药耐药性。

目的:研究异拉帕米(R-dl-verapamil, R-Ver)对多药耐药(MDR)的抑制作用及急性动物毒性，并将R-Ver与dl-verapamil (Ver)的结果进行比较。方法:采用四氮唑(MTT)法测定细胞毒性。荧光分光光度法测定阿霉素(Dox)的细胞积累。对BALB/c小鼠进行急性动物毒性实验。结果:R-Ver能减弱KBv200细胞对长春新碱(VCR)和Dox的MDR。这种衰减能力与剂量有关，也取决于药物暴露时间。R-Ver 1.25 μ mol。L-1增加KBv200细胞对VCR的敏感性(P < 0.01)。R-Ver下调MDR和增加KBv200细胞的Dox积累与Ver一样有效，但在BALB/c小鼠中具有较低的急性毒性。而Ver的LD50为60 (49 ~ 73)mg。R-Ver的LD50为166 (137-202)mg.kg-1。结论:R-Ver在1.25 μ mol时下调MDR至VCR和Dox。L-1，这种对VCR的影响可以在药物暴露时间为24 h时实现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Zhongguo yao li xue bao = Acta pharmacologica Sinica

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