Leukemia is the most common childhood
cancer.
Trisenox, the active ingredient of which is trivalent
arsenic, is the first line of treatment for
acute promyelocytic leukemia. Since
drug action usually requires uptake of the
drug, it is of importance to determine the transport system responsible for
Trisenox uptake. Recently, human
aquaglyceroporin 9 (AQP9) has been shown to transport As(III) in Xenopus oocytes. In this study we report to show that AQP9 expression modulates the
drug sensitivity of leukemic cells. AQP9 was transfected into the
chronic myelogenous leukemia cell line K562. The transfectants became hypersensitive to
Trisenox and Sb(III). The promyelocytic
leukemia cell line HL60 treated with
vitamin D showed higher expression of AQP9 and
hypersensitivity to
Trisenox and Sb(III). This sensitivity was due to higher rates of uptake of the trivalent
metalloids by the cell lines overexpressing AQP9.
Trisenox hypersensitivity results from increased expression of AQP9
drug uptake system. The possibility of using pharmacological agents to increase expression of AQP9 gene delivers the promise of new
therapies for the treatment of
leukemia. Thus,
drug hypersensitivity can be correlated with increased expression of the
drug uptake system. This is the first demonstration that AQP9 can modulate
drug sensitivity in
cancer.