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

作　　者：张维义[1] 夏维 苑广超 王芳[1] 江辉[2] 范李[3] ZHANG Weiyi;XIA Wei;YUAN Guangchao(Department of Anesthesia,Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430000,China;不详)

机构地区：[1]武汉市中医医院麻醉科,430000 [2]华中科技大学同济医学院附属同济医院麻醉科 [3]华中科技大学同济医学院附属协和医院骨科

出　　处：《临床外科杂志》2021年第10期985-989,共5页Journal of Clinical Surgery

基　　金：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)。

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。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.

关 键 词：肝细胞癌 七氟烷 侵袭迁移 糖酵解 非编码RNA 

分 类 号：R735.7[医药卫生—肿瘤] R614[医药卫生—临床医学]