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体外冲击波与细胞毒性药物的相互作用。

In vitro interaction of lithotripter shock waves and cytotoxic drugs.

作者信息

Gambihler S, Delius M

机构信息

Institute for Surgical Research, Klinikum Grosshadern, University of Munich, Federal Republic of Germany.

出版信息

Br J Cancer. 1992 Jul;66(1):69-73. doi: 10.1038/bjc.1992.218.

Abstract

The effect of a combination of lithotripter shock waves and cytotoxic drugs was examined in vitro. L1210 cells in suspension were exposed to shock waves during incubation with cislatin, doxorubicin, daunorubicin, THP-doxorubicin, or aclacinomycin. Proliferation was determined using the 3-4,5 dimethylthiazol-2,5 diphenyl tetrazolium bromide assay. Dose enhancement ratios were calculated for each drug in order to determine the effect of the additional exposure to shock waves. In addition, partition coefficients and IC50s of the drugs were determined. It was found, that the dose enhancement ratios increased for the drugs with decreasing cytotoxicity. The effect of all five drugs was enhanced by shock waves to a higher degree at 7 min incubation as compared to 50 min incubation. The effect of cisplatin was most significantly enhanced, with a dose enhancement ratio of 6.7 at 7 min incubation. The enhancement increased with the operating voltage used for generating the shock waves, and was only present when cells were exposed to shock waves during the incubation with the drug. An increase in cellular membrane permeability is proposed as the mechanism of interaction between shock waves and drugs.

摘要

在体外研究了碎石机冲击波与细胞毒性药物联合使用的效果。将悬浮状态的L1210细胞在与顺铂、阿霉素、柔红霉素、吡柔比星或阿克拉霉素孵育期间暴露于冲击波。使用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐法测定细胞增殖。计算每种药物的剂量增强率,以确定额外暴露于冲击波的效果。此外,还测定了药物的分配系数和半数抑制浓度(IC50)。结果发现,细胞毒性降低的药物其剂量增强率增加。与孵育50分钟相比,在孵育7分钟时,冲击波对所有五种药物的作用增强程度更高。顺铂的作用增强最为显著,在孵育7分钟时剂量增强率为6.7。增强作用随用于产生冲击波的操作电压增加而增加,且仅在细胞与药物孵育期间暴露于冲击波时才出现。有人提出细胞膜通透性增加是冲击波与药物相互作用的机制。

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