七氟烷通过BACE1-AS和糖酵解途径抑制肝癌细胞的增殖及侵袭迁移

doi:10.3969/j.issn.1005-6483.2021.10.025

临床外科杂志 ›› 2021, Vol. 29 ›› Issue (10): 985-989.doi: 10.3969/j.issn.1005-6483.2021.10.025

七氟烷通过BACE1-AS和糖酵解途径抑制肝癌细胞的增殖及侵袭迁移

430000 武汉市中医医院麻醉科(张维义、苑广超、王芳)；华中科技大学同济医学院附属同济医院麻醉科(夏维、江辉)；华中科技大学同济医学院附属协和医院骨科(范李)

出版日期:2021-10-20 发布日期:2021-10-20
通讯作者: 范李，Email：fanleeeee@163.com
基金资助:
中央高校基本科研业务费专项资金资助(2020kfyXGYJ077)；湖北省卫生与计划生育委员会自然科学研究基金(WJ2017M083)；华中科技大学同济医学院第二临床学院教学研究基金(201818)

Sevoflurane inhibits the proliferation,invasion and migration of hepatocellular carcinoma cells through BACE1-AS and glycolysis

*Department of Anesthesia,Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430000,China

Online:2021-10-20 Published:2021-10-20

摘要/Abstract

摘要： 目的分析七氟烷对肝癌细胞增殖、凋亡、侵袭迁移、糖酵解以及BACE1反义RNA(BACE1-AS)表达的影响。
方法培养肝癌细胞，经过4%七氟烷处理后，用CCK-8方法检测肝癌细胞细胞增殖，用流式细胞检测细胞凋亡、用Transwell和划痕实验检测细胞侵袭和迁移，利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库对BACE1-AS的相关生物学信息进行挖掘，包括肝癌组织中的BACE1-AS表达量，预后相关分析等。
结果七氟烷刺激明显降低HepG2细胞的存活率(P＜0.05)。此外，七氟烷是一种有效的促凋亡因子(P＜0.05)；Transwell实验表明，与未处理细胞相比，七氟烷刺激明显降低HepG2细胞的侵袭力(P＜0.05)。划痕实验表明，经过七氟烷处理，HepG2细胞的迁移能力下降(P＜0.05)；七氟烷刺激明显降低HepG2细胞的葡萄糖摄取以及乳酸的生成(P＜0.05)。经过七氟烷处理后，HepG2细胞的细胞外酸化(ECAR)明显下降，而耗氧量(OCR)明显上升(P＜0.05),BACE1-AS在肝癌组织中，不管是配对样本，还是非配对样本中的表达均高于对照组织(P＜0.05)。预后分析表明，高表达BACE1-AS的肝癌病人生存期更短，风险比达1.75(P＜0.05)。BACE1-AS在3种肝癌细胞中的表达高于正常肝细胞(P＜0.05)，而经过七氟烷处理后，肝癌细胞BACE1-AS的表达明显降低(P＜0.05)。
结论 BACE1-AS是一个肝细胞癌相关癌基因，七氟烷通过抑制BACE1-AS的表达，抑制肝癌细胞的增殖、侵袭迁移和糖酵解，同时促进其凋亡，七氟烷有望用于肝癌的辅助治疗。

关键词: 肝细胞癌, 七氟烷, 侵袭迁移, 糖酵解, 非编码RNA

Abstract: Objective To investigate the effects of Sevoflurane on proliferation,apoptosis,invasion and migration,glycolysis and expression of BACE1 antisense RNA(BACE1-AS) in hepatocellular carcinoma(HCC)cells.
Methods HCC cells were cultured and treated with 4% Sevoflurane.The Cancer Genome Atlas(TCGA) was used to mine the relevant biological information of BACE1-AS,including expression in HCC tissue,prognosis correlation analysis and so on.
Results Our date showed that Sevoflurane significantly decreased the survival rate of HepG2 cells(P＜0.05).In addition,Sevoflurane was an effective pro-apoptotic factor(P＜0.05).Transwell showed that Sevoflurane decreased the invasiveness of HCC cells(P＜0.05).The scratch test showed that the migration of HepG2 cells decreased after Sevoflurane treatment,with decreased glucose uptake and lactic acid production(P＜0.05).Meanwhile,the extracellular acidified(ECAR) decreased significantly,while the oxygen consumption(OCR) increased(P＜0.05).The expression of BACE1-AS in HCC tissues was significantly higher than that in control(P＜0.05).In addition,prognostic analysis showed that the survival time of patients with high expression of BACE1-AS was significantly shorter，the hazard ratio was 1.75(P＜0.05).The expression of BACE1-AS in three kinds of HCC cells was significantly higher than that in normal hepatocytes(P＜0.05),but the expression of BACE1-AS in hepatoma cells decreased significantly after Sevoflurane treatment(P＜0.05).
Conclusion BACE1-AS is an oncogene in HCC.Sevoflurane can inhibit the proliferation,invasion,migration,glycolysis and apoptosis of HCC cells by inhibiting the expression of BACE1-AS.Sevoflurane is expected to be used as an adjuvant therapy for HCC.

Key words: hepatocellular carcinoma, Sevoflurane, invasion and migration, glycolysis, non-coding RNA

张维义夏维苑广超王芳江辉范李. 七氟烷通过BACE1-AS和糖酵解途径抑制肝癌细胞的增殖及侵袭迁移[J]. 临床外科杂志, 2021, 29(10): 985-989.

ZHANG Weiyi, XIA Wei, YUAN Guangchao, et al.. Sevoflurane inhibits the proliferation,invasion and migration of hepatocellular carcinoma cells through BACE1-AS and glycolysis[J]. JOURNAL OF CLINICAL SURGERY, 2021, 29(10): 985-989.

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七氟烷通过BACE1-AS和糖酵解途径抑制肝癌细胞的增殖及侵袭迁移

Sevoflurane inhibits the proliferation,invasion and migration of hepatocellular carcinoma cells through BACE1-AS and glycolysis

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