氧化损伤对骨髓源性肝前体细胞恶性转化的影响

文朝阳 史争鸣 赵娜 薛晓伟 丰平 王学江*

解剖学报 ›› 2015, Vol. 46 ›› Issue (6) : 780-784.

欢迎访问《解剖学报》官方网站!今天是 English
解剖学报 ›› 2015, Vol. 46 ›› Issue (6) : 780-784. DOI: 10.16098/j.issn.0529-1356.2015.06.009
肿瘤生物学

氧化损伤对骨髓源性肝前体细胞恶性转化的影响

  • 文朝阳1 史争鸣2 赵娜3 薛晓伟3 丰平3 王学江3*
作者信息 +

Effect of oxidative damage on malignant transformation of bone marrow-derived hepatic progenitor cells

  • WEN Zhao-yang1 SHI Zheng-ming2 ZHAO Na3 XUE Xiao-wei3 FENG Ping3 WANG Xue-jiang 3*
Author information +
文章历史 +

摘要

目的 探讨活性氧自由基对骨髓源性肝前体细胞恶性转化的影响。 方法 取经过鉴定的3代骨髓间充质干细胞(BMSCs)分为3组:对照组(BMSCs),生长因子诱导组(BMSCs+HGF+EGF),过氧化氢刺激组(BMSCs+HGF+EGF+ H2O2)。分别在细胞培养的第7天、14天、21天、28天用RT-PCR方法检测各组细胞的白蛋白(ALB)、甲胎蛋白(AFP)、角蛋白18 (CK18) mRNA的表达。用免疫细胞化学方法检测细胞γ-谷氨酰转酞酶(γ-GT)的表达,用Schiff染色方法检测细胞DNA含量,用流式细胞仪检测非整倍体细胞。 结果 生长因子诱导组及过氧化氢刺激组细胞有ALB mRNA、AFP mRNA及CK18 mRNA的表达,过氧化氢刺激组细胞AFP mRNA、CK18 mRNA、γ-GT的表达、DNA含量及非整倍体细胞均高于生长因子诱导组(P<0.05)。 结论 骨髓间充质干细胞在体外诱导成为肝前体细胞,活性氧自由基可促使肝前体细胞过度增殖并恶性转化。

Abstract

Objective To explore the role of oxidative damage in malignant transformation of bone marrow-derived liver stem cells. Methods Bone marrow mesenchymal stem cells (BMSCs) were divided into three groups: control group(BMSCs), GF induction group(BMSCs+GF)and Hydrogen peroxide stimulate group(BMSCs+GF+ H2O2). Albumin (ALB) mRNA, alpha-fetoprotein (AFP) mRNA and CK18 mRNA were detected by RT-PCR at 7d, 14d, 21d and 28d. Gamma glutamyl transpeptidase (γ-GT) was detected by immunocytochemical technique. DNA contents were detected by Schiff dyeing. Aneuploid somatic cells were detected by flow cytometry. Results The results of in vitro experiments showed that there were expressions of ALB mRNA, AFP mRNA and CK18mRNA in group BMSCs+GF and group BMSCs+GF+ H2O2. The expressions of AFP mRNA, CK18mRNA, γ-GT, DNA contents and aneuploid somatic cells in group BMSCs+GF+ H2O2 were higher than that in group BMSCs+GF. Conclusion Reactive oxygen species can induce bone marrow mesenchymal stem cell proliferation and malignant transformation.

关键词

骨髓间充质干细胞 / 氧化损伤 / 恶性分化 / 肝癌 / 微环境 / 反转录-聚合酶链反应 / 大鼠

Key words

Bone marrow mesenchymal stem cell / Oxidative damage / Malignant transformation / Liver cancer / Microenvironment / Reverse transcription-polymerase chain reaction / Rat

引用本文

导出引用
文朝阳 史争鸣 赵娜 薛晓伟 丰平 王学江*. 氧化损伤对骨髓源性肝前体细胞恶性转化的影响[J]. 解剖学报. 2015, 46(6): 780-784 https://doi.org/10.16098/j.issn.0529-1356.2015.06.009
WEN Zhao-yang SHI Zheng-ming ZHAO Na XUE Xiao-wei FENG Ping WANG Xue-jiang*. Effect of oxidative damage on malignant transformation of bone marrow-derived hepatic progenitor cells[J]. Acta Anatomica Sinica. 2015, 46(6): 780-784 https://doi.org/10.16098/j.issn.0529-1356.2015.06.009

参考文献

[1]Baker N, Boyette LB, Tuan RS. Characterization of bone marrow-derived mesenchymal stem cells in aging[J].Bone, 2015,70:37-47.
[2]Chivu M, Dima SO, Stancu CI, et al. In vitro hepatic differentiation of human bone marrow mesenchymal stem cells under differential exposure to liver-specific factors[J]. Transl Research, 2009, 154(3):122-132.
[3]Lacaille F. Liver tumours,toxic hepatitis, intestinal failure-associated liver disease in children[J].Clin Res Hepatol Gastroenterol, 2012, 6(3):308-310.
[4]Xiao Y, Li X, Cui Y, et al. Hydrogen peroxide inhibits proliferation and endothelial differentiation of bone marrow stem cells partially via reactive oxygen species generation[J]. Life Sci, 2014, 112(12):33-40.
[5]Sanjeev Gupta. Chapter 11-Stem Cells and Hepatocyte Transplantation. Zakim and Boyer’s Hepatology [M]. 6th ed.Philadelphia: Elsevier Inc, 2012: 157-170.
[6]Bagchi D, Swaroop A, Preuss HG, et al. Free radical scavenging,antioxidant and cancer chemoprevention by grape seed proanthocyanidin: an overview[J]. Mutat Res, 2014, 768:69-73.
[7]Marquardt JU, Factor VM, Thorgeirsson SS.Epigenetic regulation of cancer stem cells in liver cancer: Current concepts and clinical implications[J]. J Hepatol, 2010,53(3):568-577.
[8]Ke Z, Mao X, Li S, et al. Dynamic expression characteristics of Notch signal in bone marrow-derived mesenchymal stem cells during the process of differentiation into hepatocytes[J]. Tissue Cell, 2013, 45(2):95-100.
[9]Wang P, Cong M, Liu TH,et al. Primary isolated hepatic oval cells maintain progenitor cell phenotypes after two-year prolonged cultivation[J]. J Hepatol, 2010, 53(5):863-871.
[10]Pan RL, Chen Y, Xiang LX, et al. Fetal liver-conditioned medium induces hepatic specification from mouse bone marrow mesenchymal stromal cells: a novel strategy for hepatic transdifferentiation[J].Cytotherapy,2008, 10(7):668-675.
[11]Buzzanco A, Gomez A, Rodriguez E,et al. Digital quantitation of HCC-associated stem cell markers and protein quality control factors using tissue arrays of human liver sections[J]. Exp Mol Pathol, 2014, 97(3):399-410.
[12]Tsuchiya T, Wang L, Yafune A,  et al. Disruptive cell cycle regulation involving epigenetic downregulation of Cdkn2a (p16Ink4a) in early-stage liver tumor-promotion facilitating liver cell regeneration in rats[J]. Toxicology, 2012, 299(28):146-154.
[13]Weindel M, Zulfiqar M, Bhalla A, et al. Molecular diagnostics in the neoplasms of the pancreas, liver, gall bladder, and extrahepatic biliary tract[J]. Clin Lab Med, 2013, 33(4):875-880.
[14]Tan ShJ, Feng FF, Wu YJ, et al. Study of Aided Diagnosis of Hepatic Carcinoma Based on Artificial Neural Network Combined with Tumor Marker Group[J]. Physics Procedia, 2012, 33:172-178.
[15]Chatterjee R, Mitra A. An overview of effective therapies and recent advances in biomarkers for chronic liver diseases and associated liver cancer[J]. Int Immunopharmacol, 2015, 24(2):335-345.

基金

尾加压素及其受体介导卵圆细胞在肝癌形成中的作用和分子机制;北京市属高等学校创新团队建设与教师职业发展计划项目


Accesses

Citation

Detail

段落导航
相关文章

/