Aquaporins mediate the chemoresistance of human melanoma cells to arsenite

Gao, Lin; Gao, Yanhui; Li, Xiaobo; Howell, Paul; Kumar, Rajeev; Su, Xiulan; Vlassov, Alexander V.; Piazza, Gary A.; Riker, Adam I.; Sun, Dianjun; Xi, Yaguang

doi:10.1016/j.molonc.2011.11.001

« Previous Next »Molecular Oncology
Volume 6, Issue 1 , Pages 81-87, February 2012

Aquaporins mediate the chemoresistance of human melanoma cells to arsenite

Lin Gao
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China
- Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA
Yanhui Gao
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China
Xiaobo Li
- Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA
Paul Howell
- Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA
Rajeev Kumar
- Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA
Xiulan Su
- Clinical Medical Research Center of the Affiliated Hospital, Inner Mongolia Medical College, Hohhot 010050, China
Alexander V. Vlassov
- Life Technologies, Austin, TX 78744, USA
Gary A. Piazza
- Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA
Adam I. Riker
- Advocate Christ Medical Center, Advocate Cancer Institute, Oak Lawn, IL 60453, USA
Dianjun Sun
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China
- Corresponding author. Tel.: +86 451 8661 2695; fax: +86 451 8665 7674.
Yaguang Xi
- Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA
- Corresponding author. Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Ave., Mobile, AL 36604, USA. Tel.: +1 251 445 9857; fax: +1 251 460 6994.

Received 19 September 2011; received in revised form 3 November 2011; accepted 4 November 2011. published online 21 November 2011.

Abstract

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.

Highlights

► 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.

Keywords: AQP, Melanoma, Arsenite, Chemotherapy