ラット腹水肝癌細胞のビンブラスチン感受性とレセルピンによるピンブラスチン細胞内蓄積機作

概要

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The relationship between the intracellular accumulation of vinblastine (VBL) and the effect of reserpine in four rat ascites hepatoma cell lines having different sensitivities to VBL was investigated. The order of the sensitivity to VBL was AH66 cells<AH109A cells<AH44 cells<AH13 cells. The intracellular VBL content for 30 min incubation was higher in sensitive cells than in natural resistant cells and after washing out extracellular VBL, VBL retained in sensitive cells was more than that in resistant cells. Reserpine suppressed the extrusion of VBL, accumulated VBL in all cells, and enhanced VBL sensitivity of the cells. These effects of reserpine were significant in VBL resistant cell lines, AH66 cells and AH109A cells, rather than in sensitive cell lines, AH13 cells and AH44 cells, and the VBL resistance was completely overcome by reserpine. The activities of adenosine triphosphatase (ATPase), especially Mg^<2+> ATPase, in the plasma membrane of VBL resistant cells were higher than those of sensitive cells. Reserpine markedly suppressed the activities of Mg^<2+> ATPase and Ca^<2+> ATPase but had no effect on (Na^+-K^+) ATPase activity. From these results, it was indicated that rat ascites hepatoma cells possessing higher ATPase activities in the plasma membrane were more resistant to VBL and reserpine overcame the natural resistance to VBL suppressing the active efflux of VBL.
社団法人日本薬学会の論文
1984-12-25