[The extracellular pH and membrane fluidity on intracellular retention of adriamycin]

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.