Marutaka M, Iwagaki H, Aoki H, Suguri T, Tanaka N, Orita K
First Dept. of Surgery, Okayama University Medical School.
Gan To Kagaku Ryoho. 1994 Oct;21(14):2415-9.
Using flow cytometry, we evaluated the effect of extracellular pH on intracellular retention of adriamycin (ADR) in K562 cells. The intracellular retention of ADR at pH 7.60 increased markedly compared to the level at pH 7.30. The cell membrane fluidity was measured by spin labeled electron spin resonance techniques. The cell membrane fluidity at pH 7.60 decreased significantly in comparison with those at pH 7.45 and 7.30. The antiproliferative effect of ADR at pH 7.60 was significantly augmented compared to those at pH 7.45 and 7.30. These results suggested that the augmentation of ADR-induced antiproliferative effect by extracellular alkalic shift was caused by membrane rigidity of lipid bilayer, resulting in the decrease of ADR efflux due to less function of P-glycoprotein.
我们使用流式细胞术评估了细胞外pH值对阿霉素（ADR）在K562细胞内潴留的影响。与pH 7.30时相比，pH 7.60时ADR的细胞内潴留显著增加。通过自旋标记电子自旋共振技术测量细胞膜流动性。与pH 7.45和pH 7.30时相比，pH 7.60时细胞膜流动性显著降低。与pH 7.45和pH 7.30时相比，pH 7.60时ADR的抗增殖作用显著增强。这些结果表明，细胞外碱化导致ADR诱导的抗增殖作用增强是由脂质双层的膜刚性引起的，这导致P-糖蛋白功能减弱，从而减少了ADR的外排。
