摘要
Background:Hepatocellular carcinoma(HCC)is frequently associated withmetabolism dysfunction.Increasing evidence has demonstrated the crucial role of lipidmetabolismin HCC progression.The function of apolipoprotein F(ApoF),a lipid transfer inhibitor protein,in HCC is incompletely understood.We aimed to evaluate the functional role of ApoF in HCC in this study.Methods:We used quantitative reverse-transcription polymerase chain reaction(qRT-PCR)to detect ApoF mRNA expression in HCC tissues and hepatoma cell lines(SMMC-7721,HepG2,and Huh7).Immunohistochemistry was performed to detect the expression of ApoF in HCC tissues.The associations between ApoF expression and clinicopathological features as well as HCC prognosis were analyzed.The effect of ApoF on cellular proliferation and growth of SMMC-7721 and Huh7 cells was examined in vitro and in vivo.Results:ApoF expression was significantly down-regulated at both mRNA and protein levels in HCC tissues as compared with adjacent tissues.In SMMC-7721 and Huh7 HCC cells,ApoF overexpression inhibited cell proliferation and migration.In a xenograft nude mouse model,ApoF overexpression effectively controlled HCC growth.Kaplan–Meier analysis results showed that the recurrence-free survival rate of HCC patients with low ApoF expression was significantly lower than that of other HCC patients.Low ApoF expression was associated with several clinicopathological features such as liver cirrhosis,Barcelona Clinic Liver Cancer stage and tumor-node-metastasis stage.Conclusions:ApoF expression was down-regulated in HCC,which was associated with low recurrence-free survival rate.ApoF may serve as a tumor suppressor in HCC and be a potential application for the treatment of this disease.
背景:肝癌患者常伴有代谢异常。越来越多的证据表明,脂质代谢在肝癌进展中具有至关重要的作用。载脂蛋白F(ApoF)是一种脂质转运蛋白抑制剂,其在肝癌中的作用并不十分明了。本研究旨在评价ApoF在肝癌中的作用。方法:采用定量逆转录聚合酶链反应(qRT-PCR)方法检测肝癌组织和肝癌细胞(SMMC-7721、HepG2和Huh7)中ApoF mMRA的表达。采用免疫组化技术检测肝癌组织中ApoF蛋白表达,并分析其与肝癌患者临床病理特征及预后的关系。最后,分别在体外(SMMC-7721和Huh7肝癌细胞系)和体内试验(异种移植裸鼠模型)中检测ApoF对肝癌生长的影响。结果:无论是在mRNA还是蛋白水平,ApoF在肝癌组织中的表达都显著下调。在smmc-7721和Huh7肝癌细胞中,ApoF过表达可抑制肝癌细胞的增殖和迁移。在异种移植裸鼠模型中,ApoF过表达可有效抑制肝癌的生长。Kaplan-Meier分析结果显示,ApoF低表达的肝癌患者无复发生存率明显低于ApoF高表达者。ApoF低表达与肝硬化、巴塞罗那临床肝癌分期及TNM分期等临床病理特征显著相关。结论:ApoF在肝癌中表达下调,而其低表达提示无复发生存率不佳。作为一种肝癌抑制因子,ApoF可能成为一个潜在的肝癌治疗靶点。
基金
This study was supported by grants from the National Natural Science Foundation of China[No.81572726]
the Natural Science Foundation of Guangdong Province[No.2018A030313641 and No.2016A030313848]
the Science and Technology Planning Project of Guangdong Province[No.2014A020212122 and No.2016A020212004]
the Medical Research Foundation of Guangdong Province[No.A2016312].
