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*

doi:10.3969/j.issn.1672-5069.2024.02.003

Abstract

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 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 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 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 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.

Key words: Hepatoma, p53 apoptosis-stimulating protein 2, Diethylnitrosamine , Nuclear factor κB, Mice

Gao Minghui, Chai Mengyin, Kou Buxin, et al.. ASPP2 recombinant adenovirus inhibits DEN-induced hepatocarcinogenesis in mice by regulating NF-κB signaling pathway[J]. Journal of Practical Hepatology, 2024, 27(2): 169-172, 173.

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ASPP2 recombinant adenovirus inhibits DEN-induced hepatocarcinogenesis in mice by regulating NF-κB signaling pathway

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