螢光色素dis-C(3)-(5)によるEhrlich腹水癌細胞の膜電位測定ならびにその内在呼吸阻害機構の解析と癌治療への応用

Changes in fluorescent intensity of the cyanine dye, 3,3'-dipropyl-2,2'-thiodicarbocyanine iodide [diS-C(3)-(5)], were monitored in Ehrlich ascites tumor cells (EATC) in correlation with glycolytic energy metabolism and endogenous respiration. After addition of glucose to EATC, membrane potentials monitored by diS-C(3)-(5) increased. The cyanine dyes were incorporated into EATC in proportion to the membrane potentials, and inhibited the endogenous respiration of EATC by more than 85% at a concentration of 100 μM. The inhibited respiration was partially released by addition of an uncoupler of oxidative phosphorylation (DNP). The respiratory activity of NAD-linked substrates in mitochondria (2.7 mg protein/ml) was also inhibited by diS-C(3)-(5), which inhibited the Rotenone-sensitive sites of the respiratory chains (Site 1) and increased Mg(++)ATPase activity. The inhibition by diS-C(3)-(5) of endogenous respiration in EATC in vivo was also effective even 24 hours after administration of the dye into the peritoneal cavity. The mean survival times of EATC-bearing mice were significantly prolonged by the administration of diS-C(3)-(5). The data suggest that the cell membrane potential is a useful factor when administering therapeutic drugs into target cells.