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Aging (Albany NY). 2019 May 8;11(9):2681-2698. doi: 10.18632/aging.101940.

Magnesium transporter protein solute carrier family 41 member 1 suppresses human pancreatic ductal adenocarcinoma through magnesium-dependent Akt/mTOR inhibition and bax-associated mitochondrial apoptosis.

Xie J1,2, Cheng CS1,2, Zhu XY1,2, Shen YH1,2, Song LB1,2, Chen H1,2, Chen Z1,2, Liu LM1,2, Meng ZQ1,2.

Author information

1
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China.
2
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P. R. China.

Abstract

The aim of this study was to identify the function of the Mg2+ transporter protein solute carrier family 41 member 1 SLC41A1 in pancreatic ductal adenocarcinoma and the underlying mechanisms. A total of 27 solute carrier proteins were differentially expressed in pancreatic ductal adenocarcinoma. Three of these proteins were correlated with clinical outcomes in patients, among which SLC41A1 was downregulated in tumour. Overexpression of SLC41A1 suppressed orthotopic tumour growth in a mouse model and reduced the cell proliferation, colony formation, and invasiveness of KP3 and Panc-1 cells, which may have been associated with the increased population of apoptotic-prone cells. Overexpression of SLC41A1 reduced the mitochondrial membrane potential, induced Bax while suppressed Bcl-2 expression. Suppression of Bax abrogated the tumour-suppressive effects of SLC41A1. Furthermore, overexpression of SLC41A1 promoted Mg2+ efflux and suppressed Akt/mTOR activity, which is the upstream regulator of Bax and Bcl-2. An increase in Akt activity and supplementation with Mg2+ abolished SLC41A1-induced tumour suppression. The results of this study suggest that SLC41A1 may be a potential target for the treatment of pancreatic ductal adenocarcinoma.

KEYWORDS:

Akt/mTOR; ROS; SLC41A1; age-related disease; aging; apoptosis; mitochondira membrane potential; pancreatic ductal adenocarcinoma

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