Overexpression of PCK1 Gene Antagonizes Hepatocellular Carcinoma Through the Activation of Gluconeogenesis and Suppression of Glycolysis Pathways
Background/Aims: Gluconeogenesis, a reverse process of glycolysis, is suppressed in neoplastic livers. Cytoplasmic phosphoenolpyruvate carboxykinase (PEPCK-C/PCK1, encoded by PCK1) is a step limiting enzyme of gluconeogenesis. The induced expression of the factor is reported to initiate gluconeogene...
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Cell Physiol Biochem Press GmbH & Co KG
2018-05-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/489811 |
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| author | Yufu Tang Yibing Zhang Chunhui Wang Zhongyi Sun Longfei Li Shuqun Cheng Wenping Zhou |
| author_facet | Yufu Tang Yibing Zhang Chunhui Wang Zhongyi Sun Longfei Li Shuqun Cheng Wenping Zhou |
| author_sort | Yufu Tang |
| collection | DOAJ |
| description | Background/Aims: Gluconeogenesis, a reverse process of glycolysis, is suppressed in neoplastic livers. Cytoplasmic phosphoenolpyruvate carboxykinase (PEPCK-C/PCK1, encoded by PCK1) is a step limiting enzyme of gluconeogenesis. The induced expression of the factor is reported to initiate gluconeogenesis process and antagonize hepatocellular carcinoma (HCC). In the current study, the effect of the modulation of PCK1 expression on HCC was assessed. Methods: The levels of PCK1 in clinical HCC tissues and different HCC cell lines were investigated with real time quantitative PCR, immunochemistry, and western blotting. Thereafter, the expression of PCK1 gene was induced in two HCC cell lines and the effect of the overexpression on proliferation and migration potentials of HCC cells was detected with CCK-8 assay, flow cytometry, TUNEL staining, and transwell assay. The activities of glycolysis and gluconeogenesis pathways in PCK1-overexpressed HCC cell lines were detected with specific kits to underlie the mechanism by which PCK1 exerted its function. The results of the in vitro experiments were validated with HCC xenograft rat models. Results: The expression levels of PCK1 were suppressed in HCC samples and in cells derived from HCC tissues. According to the results of the in vitro assays, the overexpression of PCK1 decreased viability, induced apoptosis, and inhibited migration in both HCC cell lines. The effect was associated with the suppressed glycolysis and the induced gluconeogenesis pathways, represented by the enhanced production of glucose and the limited production of pyruvic acid, lactate, citrate, and malate. The results of the in vitro assays were confirmed in rat models in that the growth rate of solid HCC tumors was reduced in mice transplanted with PCK1-overexpressed HCC cells. Conclusion: Findings outlined in the current study demonstrated that activating gluconeogenesis process via PCK1 overexpression was a potential treating strategy against HCC. |
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| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-21T19:12:13Z |
| publishDate | 2018-05-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
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| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-645ad713cab046f6b645b31a78fdf97d2022-12-21T18:53:10ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-05-0147134435510.1159/000489811489811Overexpression of PCK1 Gene Antagonizes Hepatocellular Carcinoma Through the Activation of Gluconeogenesis and Suppression of Glycolysis PathwaysYufu TangYibing ZhangChunhui WangZhongyi SunLongfei LiShuqun ChengWenping ZhouBackground/Aims: Gluconeogenesis, a reverse process of glycolysis, is suppressed in neoplastic livers. Cytoplasmic phosphoenolpyruvate carboxykinase (PEPCK-C/PCK1, encoded by PCK1) is a step limiting enzyme of gluconeogenesis. The induced expression of the factor is reported to initiate gluconeogenesis process and antagonize hepatocellular carcinoma (HCC). In the current study, the effect of the modulation of PCK1 expression on HCC was assessed. Methods: The levels of PCK1 in clinical HCC tissues and different HCC cell lines were investigated with real time quantitative PCR, immunochemistry, and western blotting. Thereafter, the expression of PCK1 gene was induced in two HCC cell lines and the effect of the overexpression on proliferation and migration potentials of HCC cells was detected with CCK-8 assay, flow cytometry, TUNEL staining, and transwell assay. The activities of glycolysis and gluconeogenesis pathways in PCK1-overexpressed HCC cell lines were detected with specific kits to underlie the mechanism by which PCK1 exerted its function. The results of the in vitro experiments were validated with HCC xenograft rat models. Results: The expression levels of PCK1 were suppressed in HCC samples and in cells derived from HCC tissues. According to the results of the in vitro assays, the overexpression of PCK1 decreased viability, induced apoptosis, and inhibited migration in both HCC cell lines. The effect was associated with the suppressed glycolysis and the induced gluconeogenesis pathways, represented by the enhanced production of glucose and the limited production of pyruvic acid, lactate, citrate, and malate. The results of the in vitro assays were confirmed in rat models in that the growth rate of solid HCC tumors was reduced in mice transplanted with PCK1-overexpressed HCC cells. Conclusion: Findings outlined in the current study demonstrated that activating gluconeogenesis process via PCK1 overexpression was a potential treating strategy against HCC.https://www.karger.com/Article/FullText/489811GluconeogenesisGlycolysisHepatocellular carcinomaPhosphoenolpyruvate carboxykinase 1 |
| spellingShingle | Yufu Tang Yibing Zhang Chunhui Wang Zhongyi Sun Longfei Li Shuqun Cheng Wenping Zhou Overexpression of PCK1 Gene Antagonizes Hepatocellular Carcinoma Through the Activation of Gluconeogenesis and Suppression of Glycolysis Pathways Cellular Physiology and Biochemistry Gluconeogenesis Glycolysis Hepatocellular carcinoma Phosphoenolpyruvate carboxykinase 1 |
| title | Overexpression of PCK1 Gene Antagonizes Hepatocellular Carcinoma Through the Activation of Gluconeogenesis and Suppression of Glycolysis Pathways |
| title_full | Overexpression of PCK1 Gene Antagonizes Hepatocellular Carcinoma Through the Activation of Gluconeogenesis and Suppression of Glycolysis Pathways |
| title_fullStr | Overexpression of PCK1 Gene Antagonizes Hepatocellular Carcinoma Through the Activation of Gluconeogenesis and Suppression of Glycolysis Pathways |
| title_full_unstemmed | Overexpression of PCK1 Gene Antagonizes Hepatocellular Carcinoma Through the Activation of Gluconeogenesis and Suppression of Glycolysis Pathways |
| title_short | Overexpression of PCK1 Gene Antagonizes Hepatocellular Carcinoma Through the Activation of Gluconeogenesis and Suppression of Glycolysis Pathways |
| title_sort | overexpression of pck1 gene antagonizes hepatocellular carcinoma through the activation of gluconeogenesis and suppression of glycolysis pathways |
| topic | Gluconeogenesis Glycolysis Hepatocellular carcinoma Phosphoenolpyruvate carboxykinase 1 |
| url | https://www.karger.com/Article/FullText/489811 |
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