水通道蛋白介导人黑色素瘤细胞对砷剂的化学耐药性。
Aquaporins mediate the chemoresistance of human melanoma cells to arsenite.
机构信息
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China.
出版信息
Mol Oncol. 2012 Feb;6(1):81-7. doi: 10.1016/j.molonc.2011.11.001. Epub 2011 Nov 13.
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.
水通道蛋白（AQP）是一种整合膜通道蛋白，在各种人类癌症中具有癌基因特征的异常表达。在这项研究中，我们分析了所有亚型 AQP 的表达模式，发现黑色素瘤细胞中表达了 13 种 AQP 中的 8 种。为了了解 AQP 异常表达在这种疾病中的作用，我们在人黑色素瘤 WM266.4 细胞中转染了 AQP3 和 AQP9，发现这两种 AQP 均显著增加了 WM266.4 细胞对亚砷酸盐的化疗耐药性。功能研究表明，AQP3 和 AQP9 通过下调 p53 和上调 Bcl-2 和 XIAP 抑制亚砷酸盐诱导的细胞凋亡。我们的数据表明 AQP 在黑色素瘤进展中的作用，并且 AQP3 和 AQP9 的过表达有助于黑色素瘤对亚砷酸盐的化疗耐药性。
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