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Wortmannin influences hypoxia-inducible factor-1 alpha expression and glycolysis in esophageal carcinoma cells.
World J Gastroenterol 2016; 22(20):4868-80WJ

Abstract

AIM

To investigate the influence of phosphatidylinositol-3-kinase protein kinase B (PI3K/AKT)-HIF-1α signaling pathway on glycolysis in esophageal carcinoma cells under hypoxia.

METHODS

Esophageal carcinoma cell lines Eca109 and TE13 were cultured under hypoxia environment, and the protein, mRNA and activity levels of hypoxia inducible factor-1 alpha (HIF-1α), glucose transporter 1, hexokinase-II, phosphofructokinase 2 and lactate dehydrogenase-A were determined. Supernatant lactic acid concentrations were also detected. The PI3K/AKT signaling pathway was then inhibited with wortmannin, and the effects of hypoxia on the expression or activities of HIF-1α, associated glycolytic enzymes and lactic acid concentrations were observed. Esophageal carcinoma cells were then transfected with interference plasmid with HIF-1α-targeting siRNA to assess impact of the high expression of HIF-1α on glycolysis.

RESULTS

HIF-1α is highly expressed in the esophageal carcinoma cell lines tested, and with decreasing levels of oxygen, the expression of HIF-1α and the associated glycolytic enzymes and the extracellular lactic acid concentration were enhanced in the esophageal carcinoma cell lines Eca109 and TE13. In both normoxia and hypoxic conditions, the level of glycolytic enzymes and the secretion of lactic acid were both reduced by wortmannin. The expression and activities of glycolytic enzymes and the lactic acid concentration in cells were reduced by inhibiting HIF-1α, especially the decreasing level of glycolysis was significant under hypoxic conditions.

CONCLUSION

The PI3K/AKT pathway and HIF-1α are both involved in the process of glycolysis in esophageal cancer cells.

Authors+Show Affiliations

Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27239113

Citation

Zeng, Ling, et al. "Wortmannin Influences Hypoxia-inducible Factor-1 Alpha Expression and Glycolysis in Esophageal Carcinoma Cells." World Journal of Gastroenterology, vol. 22, no. 20, 2016, pp. 4868-80.
Zeng L, Zhou HY, Tang NN, et al. Wortmannin influences hypoxia-inducible factor-1 alpha expression and glycolysis in esophageal carcinoma cells. World J Gastroenterol. 2016;22(20):4868-80.
Zeng, L., Zhou, H. Y., Tang, N. N., Zhang, W. F., He, G. J., Hao, B., ... Zhu, H. (2016). Wortmannin influences hypoxia-inducible factor-1 alpha expression and glycolysis in esophageal carcinoma cells. World Journal of Gastroenterology, 22(20), pp. 4868-80. doi:10.3748/wjg.v22.i20.4868.
Zeng L, et al. Wortmannin Influences Hypoxia-inducible Factor-1 Alpha Expression and Glycolysis in Esophageal Carcinoma Cells. World J Gastroenterol. 2016 May 28;22(20):4868-80. PubMed PMID: 27239113.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Wortmannin influences hypoxia-inducible factor-1 alpha expression and glycolysis in esophageal carcinoma cells. AU - Zeng,Ling, AU - Zhou,Hai-Yun, AU - Tang,Na-Na, AU - Zhang,Wei-Feng, AU - He,Gui-Jun, AU - Hao,Bo, AU - Feng,Ya-Dong, AU - Zhu,Hong, PY - 2015/10/10/received PY - 2016/03/20/revised PY - 2016/04/15/accepted PY - 2016/5/31/entrez PY - 2016/5/31/pubmed PY - 2017/4/11/medline KW - Cell metabolism KW - Esophageal neoplasms KW - Glycolysis KW - Hypoxia KW - Hypoxia-inducible factor-1 alpha SP - 4868 EP - 80 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 22 IS - 20 N2 - AIM: To investigate the influence of phosphatidylinositol-3-kinase protein kinase B (PI3K/AKT)-HIF-1α signaling pathway on glycolysis in esophageal carcinoma cells under hypoxia. METHODS: Esophageal carcinoma cell lines Eca109 and TE13 were cultured under hypoxia environment, and the protein, mRNA and activity levels of hypoxia inducible factor-1 alpha (HIF-1α), glucose transporter 1, hexokinase-II, phosphofructokinase 2 and lactate dehydrogenase-A were determined. Supernatant lactic acid concentrations were also detected. The PI3K/AKT signaling pathway was then inhibited with wortmannin, and the effects of hypoxia on the expression or activities of HIF-1α, associated glycolytic enzymes and lactic acid concentrations were observed. Esophageal carcinoma cells were then transfected with interference plasmid with HIF-1α-targeting siRNA to assess impact of the high expression of HIF-1α on glycolysis. RESULTS: HIF-1α is highly expressed in the esophageal carcinoma cell lines tested, and with decreasing levels of oxygen, the expression of HIF-1α and the associated glycolytic enzymes and the extracellular lactic acid concentration were enhanced in the esophageal carcinoma cell lines Eca109 and TE13. In both normoxia and hypoxic conditions, the level of glycolytic enzymes and the secretion of lactic acid were both reduced by wortmannin. The expression and activities of glycolytic enzymes and the lactic acid concentration in cells were reduced by inhibiting HIF-1α, especially the decreasing level of glycolysis was significant under hypoxic conditions. CONCLUSION: The PI3K/AKT pathway and HIF-1α are both involved in the process of glycolysis in esophageal cancer cells. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/27239113/Wortmannin_influences_hypoxia_inducible_factor_1_alpha_expression_and_glycolysis_in_esophageal_carcinoma_cells_ L2 - http://www.wjgnet.com/1007-9327/full/v22/i20/4868.htm DB - PRIME DP - Unbound Medicine ER -