Asaumi J, Kawasaki S, Nishikawa K, Kuroda M, Hiraki Y
Department of Radiology, Okayama University Medical School, Japan.
Anticancer Res. 1995 Jan-Feb;15(1):71-5.
We examined the influence of the extracellular pH, an inhibitor of Na+/H+ exchanger: 3,5-diamino-6-chloro-N-(diaminomethylene) pyrazinecarboxamide (amiloride), and an inhibitor of Cl-/HCO3-: 4,4 -diisothiocyanatostilbene -2,2 -disulfonic acid (DIDS) on the accumulation of adriamycin (ADR) in Ehrlich ascites tumor cells and their adriamycin-resistant strain. A good correlation between the increases in ADR accumulation and the extracellular pH was shown in the both strains. The ADR accumulation decreased with an increasing concentration of amiloride or DIDS in both strains. These findings demonstrate that the influx of ADR was related closely to the efflux of H+ or to the activities of Na+/H+ ex-changer and Cl-/HCO3-exchanger. Therefore, raising the extracellular pH and enhancement of the activities of either Na+/H+ exchanger or Cl-/HCO3-exchanger may result in the potentiation of the cytotoxic effect of ADR through increase of ADR influx.
我们研究了细胞外pH值、一种Na⁺/H⁺交换体抑制剂：3,5-二氨基-6-氯-N-(二氨基亚甲基)吡嗪甲酰胺（氨氯吡咪）以及一种Cl⁻/HCO₃⁻抑制剂：4,4'-二异硫氰酸根合芪-2,2'-二磺酸（DIDS）对阿霉素（ADR）在艾氏腹水瘤细胞及其阿霉素耐药株中蓄积的影响。在这两种细胞株中，ADR蓄积的增加与细胞外pH值之间均呈现良好的相关性。在两种细胞株中，随着氨氯吡咪或DIDS浓度的增加，ADR的蓄积均减少。这些发现表明，ADR的内流与H⁺外流或与Na⁺/H⁺交换体及Cl⁻/HCO₃⁻交换体的活性密切相关。因此，提高细胞外pH值以及增强Na⁺/H⁺交换体或Cl⁻/HCO₃⁻交换体的活性可能会通过增加ADR内流而导致ADR细胞毒性作用的增强。
