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路欣, 孔令玉, 贾蕾, 姜玲玲. D-双功能蛋白通过STAT3促进大鼠肝细胞肝癌的形成机制[J]. 肿瘤防治研究, 2019, 46(8): 690-695. DOI: 10.3971/j.issn.1000-8578.2019.19.0170
引用本文: 路欣, 孔令玉, 贾蕾, 姜玲玲. D-双功能蛋白通过STAT3促进大鼠肝细胞肝癌的形成机制[J]. 肿瘤防治研究, 2019, 46(8): 690-695. DOI: 10.3971/j.issn.1000-8578.2019.19.0170
LU Xin, KONG Lingyu, JIA Lei, JIANG Lingling. Mechanism of D-bifunctional Protein Promoting Formation of Hepatocellular Carcinoma in Rat via STAT3[J]. Cancer Research on Prevention and Treatment, 2019, 46(8): 690-695. DOI: 10.3971/j.issn.1000-8578.2019.19.0170
Citation: LU Xin, KONG Lingyu, JIA Lei, JIANG Lingling. Mechanism of D-bifunctional Protein Promoting Formation of Hepatocellular Carcinoma in Rat via STAT3[J]. Cancer Research on Prevention and Treatment, 2019, 46(8): 690-695. DOI: 10.3971/j.issn.1000-8578.2019.19.0170

D-双功能蛋白通过STAT3促进大鼠肝细胞肝癌的形成机制

Mechanism of D-bifunctional Protein Promoting Formation of Hepatocellular Carcinoma in Rat via STAT3

  • 摘要:
    目的 探讨大鼠肝癌组织中D-双功能蛋白(DBP)的表达及其与信号转导子和转录激活子3(STAT3)活化的相关性。
    方法 腹腔注射二乙基亚硝胺(DEN)诱导大鼠肝细胞肝癌(HCC)模型。HE染色和血清生化指标检测HCC大鼠肝脏病理恶化程度,蛋白免疫印迹、免疫组织化学和qRT-PCR检测DBP、PCNA、cyclinD1、p-STAT3、p-Akt、p-MEK和p-ERK的表达。计量资料两组间比较采用t检验,检测指标相关性检验采用Pearson相关分析。
    结果 DEN诱导HCC大鼠肝脏恶化严重,HCC大鼠肝脏组织中DBP的表达高于正常大鼠肝脏;HCC组PCNA和cyclin D1 mRNA的表达水平显著高于正常组,而且DBP与PCNA和cyclin D1的表达量呈正相关;在HepG2细胞中DBP过表达和敲低能相应增加和减少细胞的数量,并且引起PCNA和cyclin D1蛋白表达的增加和减少;HCC组大鼠p-STAT3表达显著增加,并且与DBP的表达水平呈正相关,同时p-Akt、p-MEK以及p-ERK的蛋白水平较正常组也显著增强。
    结论 高表达的DBP在大鼠肝癌的发展进程中发挥了促进作用。

     

    Abstract:
    Objective To investigate the expression of D-bifunctional protein (DBP) in hepatocarcinoma tissues of rat and its correlation with signal transducer and activator of transcription 3(STAT3).
    Methods Rat model of hepatocellular carcinoma(HCC) was induced by intraperitoneal injection of diethylnitrosamine(DEN). HE staining and serum biochemical indicators were used to detect liver pathological severity in HCC rats. Western blot, immunohistochemistry and qRT-PCR were used to detect the expression of DBP, PCNA, cyclinD1, p-STAT3, p-Akt, p-MEK and p-ERK.
    Results DEN induced severe liver deterioration in HCC rats. The expression of DBP in liver tissues of HCC rats was higher than that in normal rat liver. The mRNA expression of PCNA and cyclin D1 in HCC group were significantly higher than those in normal control(NC) group, and the expression of DBP was positively correlated with PCNA and cyclin D1 expression. The over-expression and knockdown of DBP increased and decreased the number of cells and the expression of PCNA, cyclin D1 protein in HepG2 cells, respectively. The expression of p-STAT3 was significantly increased in HCC group, and positively correlated with DBP expression. The protein levels of p-Akt, p-MEK and p-ERK were also significantly enhanced compared with the NC group.
    Conclusion Highly-expressed DBP plays a catalytic role in the development of rat liver cancer.

     

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