The Apoptotic Effect of HIF-1α Inhibition Combined with Glucose plus Insulin Treatment on Gastric Cancer under Hypoxic Conditions

PloS One
Tomokazu TanakaHirokazu Noshiro

Abstract

Gastric cancer grows under a hypoxic environment. HIF-1α is known to play an important role in controlling the production of reactive oxygen species (ROS) in the mitochondria under hypoxic conditions. We previously established HIF-1α knockdown (KD) cells and control (SC) cells in the 58As9 gastric cancer cell line. In this study, we revealed that KD cells, but not SC cells, induced apoptosis under conditions of hypoxia (1% O2) due to excessive production of ROS. A quantitative RT-PCR analysis demonstrated that the expressions of ten genes, which are involved in the control mechanisms of ROS (including the Warburg effect, mitophagy, electron transport chain [ETC] modification and ROS scavenging), were regulated by HIF-1α. Moreover, the promotion of glucose uptake by glucose plus insulin (GI) treatment enhanced the apoptotic effect, which was accompanied by further ROS production in hypoxic KD cells. A Western blot analysis showed that the membranous expression of GLUT1 in KD cells was elevated by glucose and/or insulin treatments, indicating that the GI-induced glucose uptake is mediated by the increased translocation of GLUT1 on the cell membrane. Finally, the anti-tumor effect of HIF-1α knockdown (KD) plus GI was evaluated usi...Continue Reading

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Citations

Jan 9, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Ying ChenDaguang Sun
Nov 29, 2016·The International Journal of Biochemistry & Cell Biology·Suvasmita RathAsima Bhattacharyya
Nov 18, 2020·Antioxidants & Redox Signaling·Zhaowu MaLingzhi Wang

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Methods Mentioned

BETA
xenograft
transfection
Assay
FACS
PCR
xenografts

Software Mentioned

Prism
Cell Quest
GraphPad
ARRIVE

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis