Vanadate is toxic to adherent-growing multidrug-resistant cells

The development of multidrug resistance (MDR) is the primary cause of failu re of cancer chemotherapy and circumventing this problem is a major challen ge in oncology. Vanadate is known to inhibit the ATPase activity of the P-g lycoprotein and multidrug-resistant associated protein. In the present stud y we show that adherent MDR cells are more sensitive to vanadate than adher ent non-MDR ones, but the same is not true for suspension-growing cells. Va nadate induced stress fiber in the non-MDR adherent MDCK cell line, but des troyed the actin fibers of MDCK/60 and MA104 cells, two adherent MDR cell l ines, suggesting that the sensitivity of these cells to vanadate is related to their actin cytoskeleton. The results suggest that vanadate may be used as an adjuvant in the chemotherapy of solid tumors, not only as an ATPase inhibitor but. also because of its effect in the MDR cell cytoskeleton. Cop yright (C) 2000 S. Karger AG. Basel.