Effects of amiloride on thermosensitivity of Chinese hamster cells under neutral and acidic pH.

Effects of amiloride on thermosensitivity of Chinese hamster cells under neutral and acidic pH.
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中性和酸性pH条件下阿米洛利对中国仓鼠细胞热敏性的影响

DOI:
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发表时间:
1986
期刊:
影响因子:
11.2
通讯作者:
C. Inagaki
C. Inagaki
中科院分区:
医学1区
文献类型:
--
作者:
J. Miyakoshi;W. Oda;M. Hirata;N. Fukuhori;C. Inagaki

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在中性(pH7.3)和酸性(pH6.6)条件下观察了阿米洛利对中国仓鼠V-79细胞温度敏感性的调节作用。阿米洛利是一种利尿药,已知可抑制Na+/H+交换活性。在细胞外pH值为7.3的条件下,随着药物浓度和暴露时间的增加,阿米洛利(0.1-0.5 mM)增强了42 ℃热疗的热细胞杀伤能力。在存在或不存在阿米洛利(0.5 mM)的情况下,细胞对42 ℃高温的年龄反应表明,阿米洛利使细胞对热敏感,特别是那些在G1-S边界通过中间S期的细胞。另一方面,将细胞外pH降低至6.6增强了42 ℃高温对细胞的杀伤。当细胞在pH6.6的阿米洛利存在下暴露于42 ℃的高温时,细胞存活率下降得更多。在6.6和阿米洛利降低pH的热敏化效果似乎是加和的。从这些结果,这表明,阿米洛利的热敏化可能是由于,在一定程度上,细胞Na+/H+交换活性的抑制。本研究提出了阿米洛利作为一种热疗增敏剂用于临床治疗癌症的可能性。
The modifying effects of amiloride on the thermosensitivity of Chinese hamster V-79 cells were examined under both neutral (pH 7.3) and acidic (pH 6.6) conditions. Amiloride, a diuretic drug, is known to inhibit the Na+/H+ exchange activity. Under the extracellular pH of 7.3, amiloride (0.1-0.5 mM) enhanced the thermal cell killing powers of 42 degrees C hyperthermia with increasing concentration and exposure time of the drug. The age response of cells to 42 degrees C hyperthermia in the presence or absence of amiloride (0.5 mM) showed that amiloride sensitized cells to heat, especially those at G1-S boundary through middle S phases. On the other hand, the lowering of extracellular pH to 6.6 enhanced cell killing by 42 degrees C hyperthermia. When cells were exposed to 42 degrees C hyperthermia in the presence of amiloride at pH 6.6, cell survival decreased still more. The thermosensitizing effects of the lowered pH at 6.6 and amiloride appeared to be additive. From these results, it is suggested that the thermosensitization by amiloride is probably due, in part, to the inhibition of cellular Na+/H+ exchange activity. The present study proposes the possibility that amiloride may be useful as a hyperthermic sensitizer in a clinical treatment of cancer.
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