烯酰辅酶A水合酶短链1、表皮生长因子及低糖环境促进肝癌细胞侵袭转移

卢嘉臻; 徐文娟; 蔡艺玲; 敖少军; 丁荣荣; 张鸣青

doi:10.3969/j.issn.1001-5256.2018.07.023

烯酰辅酶A水合酶短链1、表皮生长因子及低糖环境促进肝癌细胞侵袭转移

DOI: 10.3969/j.issn.1001-5256.2018.07.023

解放军第一七五医院消化内科

基金项目:

解放军第一七五医院院内青年苗圃基金(14Y002)；

详细信息

中图分类号: R735.7
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出版历程
- 收稿日期: 2018-01-05
- 出版日期: 2018-07-20

ECHS1, epidermal growth factor, and low-glucose conditions promote the invasion and metastasis of hepatocellular carcinoma cells

Department of Gastroenterology, 175 Hospital of PLA

Research funding:

摘要

摘要: 目的研究肝细胞癌（HCC）组织中能量代谢相关酶的表达及对肝癌细胞侵袭能力的影响,探讨烯酰辅酶A水合酶短链1（ECHS1）、AMP蛋白激酶（AMPK）、脂肪合成酶（FAS）、乙酰CoA羧化酶（ACC）等相关酶及低糖环境在HCC发生发展过程中的作用。方法选取解放军第一七五医院2015年6月-2016年6月经手术切除的32例HCC患者肝癌及癌旁组织,通过免疫组化技术,检测不同分化程度肝癌及癌旁组织中能量代谢过程中关键酶FAS、ACC及AMPK等表达情况。构建两组肝癌细胞株,对照组:转染空白对照质粒的肝癌细胞Huh7-plv、HepG2-PU6;实验组:转染小干扰RNA（siRNA）的肝癌细胞株Huh7-siECHS1、HepG2-siECHS1。应用Transwell小室实验观察ECHS1及低糖培养和加入表皮生长因子（EGF）等不同营养条件对肝癌细胞侵袭能力的影响。计量资料组间比较采用t检验;计数资料组间比较采用χ2检验。结果免疫组化结果显示,肝癌细胞中ACC、AMPKβ表达高于癌旁组织,差异均有统计学意义（21/11 vs 7/25,χ2=12....
- 癌,肝细胞 /
- 烯酰CoA水合酶 /
- 表皮生长因子 /
- 能量代谢 /
- 肿瘤侵润 /
- 肿瘤转移
Abstract: Objective To investigate the expression of key enzymes associated with energy metabolism in hepatocellular carcinoma ( HCC) tissue, as well as the roles of short-chain enoyl-CoA hydratase 1 ( ECHS1) , AMP-activated protein kinase ( AMPK) , fatty acid synthase ( FAS) , acetyl-CoA carboxylase ( ACC) , and low-glucose conditions in the development and progression of HCC. Methods A total of 32 HCC patients who underwent surgical resection in 175 Hospital of PLA from June 2015 to June 2016 were enrolled. HCC tissue and adjacent tissue samples were collected, and immunohistochemistry was used to measure the expression of key enzymes associated with energy metabolism in HCC tissue samples with different degrees of tumor differentiation and adjacent tissues, including FAS, ACC, and AMPK.Two groups of hepatoma cells were established. Hepatoma Huh7-plv and HepG2-PU6 cells transfected with blank control plasmids were established as control group, and hepatoma cells transfected with small interfering RNA ( siRNA) ( Huh7-siECHS1 and HepG2-siECHS1 cells) were established as experimental group. A Transwell chamber assay was used to observe the effect of ECHS1, low-glucose condition, and EGF on the invasion ability of hepatoma cells. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Results Immunohistochemistry showed that compared with the adjacent tissue samples, the HCC tissue samples had a significant higher proportion of ACC-or AMPKβ-positive cells ( ACC-positive cells:21/11 vs 7/25, χ2= 12. 44, P < 0. 05; AMPKβ-positive cells: 31/1 vs 26/6, χ2= 4. 68, P < 0. 05) . The Transwell chamber assay showed that compared with the corresponding hepatoma cells treated by ECHS1 interference ( Huh7-siECHS1-N, HepG2-siECHS1-N, Huh7-siECHS1-N-EGF, and HepG2-siECHS1-N-EGF) , the hepatoma cells cultured under normal conditions ( Huh7-plv-N and HepG2-PU6-N) and with the addition of EGF ( Huh7-plv-N-EGF and HepG2-PU6-N-EGF) had a significantly higher number of invasive cells ( t = 6. 93, 6. 51, 7. 55, and 4. 93, all P < 0. 05) ; compared with the corresponding hepatoma cells treated by ECHS1 interference ( Huh7-siECHS1-LowGlu, HepG2-siECHS1-LowGlu, Huh7-siECHS1-LowGlu-EGF, and HepG2-siECHS1-LowGlu-EGF) , the hepatoma cells cultured under low-glucose conditions ( Huh7-plv-LowGlu and HepG2-PU6-LowGlu) and with the addition of EGF ( Huh7-plv-LowGlu-EGF and HepG2-PU6-LowGlu-EGF) had a significantly higher number of invasive cells ( t= 9. 52, 5. 80, 20. 52, and 8. 80, all P < 0. 05) . Under different conditions, hepatoma Huh7 and HepG2 cells had a significant reduction in invasion ability after ECHS1 interference. Compared with the hepatoma cells cultured under normal conditions ( Huh7-plv-N and HepG2-PU6-N) , the hepatoma cells cultured with the addition of EGF ( Huh7-plv-N-EGF and HepG2-PU6-N-EGF) had a significant increase in the number of cells passing through the Transwell chamber ( t = 4. 44 and 3. 17, both P < 0. 05) . Compared with the hepatoma cells cultured under normal conditions, the hepatoma cells cultured under low-glucose conditions ( Huh7-plv-LowGlu and HepG2-PU6-LowGlu) had an increase in the number of invasive cells ( both P > 0. 05) . Conclusion ECHS1 and EGF can significantly enhance the invasion and metastasis of hepatoma cells, and low-glucose conditions can also promote the invasion of hepatoma cells.
- carcinoma, hepatocellular /
- enoyl-CoA hydratase /
- epidermal growth factor /
- energy metabolism /
- neoplasm invasiveness /
- neoplasm metastasis

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参考文献(21)

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