实用肝脏病杂志2024，Vol.27Issue(2)：169-173,5.DOI:10.3969/j.issn.1672-5069.2024.02.003
ASPP2重组腺病毒通过调控NF-κB信号通路抑制DEN诱导的小鼠肝细胞癌发生
ASPP2 recombinant adenovirus inhibits DEN-induced hepatocarcinogenesis in mice by regulating NF-κB signaling pathway
摘要
Abstract
Objective The aim of this experiment was to investigate the inhibitory effect of apoptosis stimulating protein 2 of P53(ASPP2)recombinant adenovirus(ASPP2-ad)on hepatocellular carcinogenesis induced by diethylnitrosamine(DEN)in mice.Methods The mouse liver cancer model was established by intraperitoneal injection of DEN at dose of 25 mg·kg-1 and drinking water with 0.005%of DEN.The experiment was divided into two groups with 10 mice in each group,receiving DEN or DEN and ASPP2-ad combination intervention.The formation of liver cancer in mice was observed by ultrasonography.The number of liver tumors was recorded,and the expression of Ki67 was detected by immunohistochemistry.Serum IL-1β,IL-6,KC,IL-2 and TNFα levels were detected by flow multiprotein quantification technology.The protein expressions of AFP,caspase3,cyclin D1,PCNA,p-IKK,IKK,p-IκB,IκB,p-p65 and p65 were observed by Western blot,and the Nfatc1 mRNA level was assayed by real-time quantitative PCR.Results After 24 weeks of DEN induction,the number of liver tumors in DEN-intervened group was(9.9±1.9),significantly greater than[(3.9±1.2),P＜0.05]in the DEN and ASPP2-ad combination intervened group;the number of Ki67 positive cells in DEN-intervened group was(91.4±9.1),significantly greater than[(56.6±10.5),P＜0.05]in DEN/ASPP2-ad-intervened group;the survival rate in the DEN-intervened group was 65.2%,significantly lower than 90.0%(P＜0.05)in DEN/ASPP2-ad-intervend group(P＜0.05);serum ALT and AST levels were(271.5±143.8)U/L and(299.3±221.4)U/L,both significantly higher than[(101.7±44.6)U/L and(124.1±75.0)U/L,P＜0.05]in DEN/ASPP2-ad-intervend group;serum IL-6 and TNFα levels in DEN/ASPP2-ad-intervend group were(8.1±1.6)MFI and(8.1±1.0)MFI,both much lower than[(16.3±0.4)MFI and(26.3±5.3)MFI,P＜0.05]in DEN-intervened group;the cancerous AFP,Cyclin D1 and PCNA expression became weaker,the p-IKK,p-IκB and p-p65 expression down-regulated,the p-IKK/IKKα,p-IκB/IκB and p-p65/p65 ratio down-regulated,the Nfatc1 expression weaker,while the caspase-3 expression intensified(P＜0.05)in DEN/ASPP2-ad-intervend group.Conclusion The ASPP2-ad could remarkably inhibit DEN-induced inflammatory proliferation reaction and the occurrence of liver cancer,which might be related to the regulation of NF-κB signal pathway,and warrants further investigation.关键词
肝细胞癌/P53凋亡刺激蛋白2/二乙基亚硝胺/核因子κB/小鼠Key words
Hepatoma/p53 apoptosis-stimulating protein 2/Diethylnitrosamine/Nuclear factor κB/Mice引用本文复制引用
高明慧,柴梦音,寇卜心,豆双双,刘晓霓..ASPP2重组腺病毒通过调控NF-κB信号通路抑制DEN诱导的小鼠肝细胞癌发生[J].实用肝脏病杂志,2024,27(2):169-173,5.基金项目
北京市自然科学基金资助项目(编号:7192084) （编号:7192084）
首都卫生发展科研专项基金资助项目(编号:2020-2-1152) （编号:2020-2-1152）
北京市公共医学研究所发展改革试点研究项目(编号:京医研2021-10) （编号:京医研2021-10）
