Effect of High Glucose on Expression of Glycolytic Enzymes in Cholangiocarcinoma Cells

Abstract

Background and Objective: Most of cholangiocarcinoma (CCA) patients are presented with metastasis which is the major cause of death of CCA patients. Understanding of factors mediated metastasis may lead to a novel treatment for CCA. Cancer cells produced most of their ATP via aerobic glycolysis. Increasing of enzymes in glycolytic pathways were reported in several cancers. The association of high glucose and CCA progression have been demonstrated previously. Thus, the aim of this study was to investigate whether high glucose condition could affect expression of glycolytic enzymes in CCA.

Methods: Three CCA cell lines, KKU-213, -214, and -055, in normal glucose condition (NG; 5.6 mM) were established by sequentially reduced glucose concentration in the media from high glucose (HG; 25 mM) to 5.6 mM. The increase of O-GlcNAcylated proteins was used as the marker indicating adaptation of cells in low or high glucose condition. Expression of glycolytic enzymes were determined using western blot.  

Results: Three CCA cell lines, KKU-213, -214, and -055, in NG and HG were successfully established. All NG cells had lower levels of O-GlcNAcylated proteins than HG cells. The western blot analysis of the key regulatory enzymes: HKII, PFK-1, PKM2, LDHA and MCT1 and MCT4 were compared between NG and HG cells. The results showed that HKII and PFK1 were increased in HG cells of both KKU-055 and KKU-213 cells.

Conclusion: High glucose could promote expression of HKII and PFK1 in CCA cells. This may be one of the mechanisms that high glucose activated progression of CCA.