Aquaporins mediate the chemoresistance of human melanoma cells to arsenite

The integral membrane channel protein aquaporin (AQP) is aberrantly expressed with oncogenic characteristics in various human cancers. In this study, we analyzed the expression pattern of all subtypes of AQPs, and found that 8 out of 13 AQPs expressed in melanoma cells. To understand the role of aberrant expression of AQP in this disease, we over-expressed AQP3 and AQP9 in human melanoma WM266.4 cells and found that both AQPs significantly increased the chemoresistance of WM266.4 cells to arsenite. Functional studies showed that AQP3 and AQP9 can inhibit cell apoptosis induced by arsenite through down-regulating p53 and up-regulating Bcl-2 and XIAP. Our data suggest the implication of APQ in melanoma progression and that the over-expression of AQP3 and AQP9 contributes to the chemoresistance of melanoma to arsenite.

► We identify the expression pattern of all subtypes of AQP in melanoma cells. ► Over-expression of AQP3 and AQP9 increases the chemoresistance of melanoma cells to arsenite. ► AQP has no effect on melanoma cell growth. ► The mechanism of AQP affecting melanoma chemoresistance is relevant to apoptosis regulated by p53, Bax, Bcl-2, and XIAP.