Reversal of the Warburg effect with DCA in PDGF‑treated human PASMC is potentiated by pyruvate dehydrogenase kinase‑1 inhibition mediated through blocking Akt/GSK‑3β signalling

International Journal of Molecular Medicine
Bingbing LiJie Yan

Abstract

There is accumulating evidence indicating that the growth inhibitory effect of dichloroacetate (DCA) on pulmonary arterial smooth muscle cells (PASMCs) may be associated with the reversal of the Warburg effect and initiation of the mitochondria‑dependent apoptotic pathway. Previous studies indicated that platelet‑derived growth factor (PDGF) promoted the Warburg effect and resulted in apoptotic resistance of PASMCs, which was attributed to activation of the phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) signalling pathway. However, the mechanism underlying the pro‑apoptotic effect of DCA on PDGF‑treated PASMCs has not been thoroughly elucidated, and the effect of the Akt/glycogen synthase kinase‑3β (GSK‑3β) pathway inhibition concomitant with the effect of DCA on PASMC proliferation remains unclear. The growth of human PASMCs and the lactate concentration in extracellular medium of PASMCs were detected by Cell Counting Kit‑8 assays and a Lactate Colorimetric Assay kit, respectively. Cell apoptosis was evaluated by fluorescence activated cell sorting. The mitochondrial membrane potential (ΔΨm) was assessed with 5,5',6,6'‑tetrachloro‑1,1',3,3'‑tetraethylbenzimidazol‑carbocyanine iodide assays. The expression levels o...Continue Reading

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Citations

Feb 13, 2020·Frontiers in Endocrinology·Wen-Ning XuSheng-Dan Jiang
Jul 3, 2021·Oxidative Medicine and Cellular Longevity·Liduo YueLihong Fan
Jul 10, 2021·Oxidative Medicine and Cellular Longevity·Judith Bernal-RamírezGerardo García-Rivas

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Methods Mentioned

BETA
fluorescence activated cell sorting
FACS
Assay
Protein Assay
X-ray
xenograft

Software Mentioned

FlowJo
GraphPad
GraphPad Prism
ImageJ

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