Article

Aspirin inhibits the proliferation of hepatoma cells through controlling GLUT1-mediated glucose metabolism

Authors: Yun-xia Liu1, Jin-yan Feng1, Ming-ming Sun1, Bo-wen Liu2, Guang Yang1, Ya-nan Bu1, Man Zhao1, Tian-jiao Wang2, Wei-ying Zhang1, Hong-feng Yuan1, Xiao-dong Zhang1
1 Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China
2 Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, China
DOI: 10.1038/s41401-018-0014-x
Received: 23 October 2017
Accepted: 31 January 2018
Advance online: 20 June 2018

Abstract

Aspirin can efficiently inhibit liver cancer growth, but the mechanism is poorly understood. In this study, we report that aspirin modulates glucose uptake through downregulating glucose transporter 1 (GLUT1), leading to the inhibition of hepatoma cell proliferation. Our data showed that aspirin significantly decreased the levels of reactive oxygen species (ROS) and glucose consumption in hepatoma cells. Interestingly, we identified that GLUT1 and HIF1α could be decreased by aspirin. Mechanically, we demonstrated that the -1008/-780 region was the regulatory element of transcriptional factor NF-κB in GLUT1 promoter by luciferase report gene assays. PDTC, an inhibitor of NF-κB, could suppress the expression of GLUT1 in HepG2 and H7402 cells, followed by affecting the levels of ROS and glucose consumption. CoCl2-activated HIF1α expression could slightly rescue the GLUT1 expression inhibited by aspirin or PDTC, suggesting that aspirin depressed GLUT1 through targeting NF-κB or NF-κB/HIF1α signaling. Moreover, we found that GLUT1 was highly expressed in clinical HCC tissues relating to their paired adjacent normal tissues. Importantly, we observed that high level of GLUT1 was significantly correlated with the poor relapse-free survival of HCC patients by analysis of public data. Functionally, overexpression of GLUT1 blocked the PDTC-induced or aspirin-induced inhibition of glucose metabolism in HepG2 cells. Conversely, aspirin failed to work when GLUT1 was stably knocked down in the cells. Administration of aspirin could depress the growth of hepatoma cells through controlling GLUT1 in vitro and in vivo. Thus, our finding provides new insights into the mechanism by which aspirin depresses liver cancer.
Keywords: aspirin; glucose uptake; GLUT1; NF-κB; liver cancer

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