活性维生素D3联合LY294002体外抑制大鼠肝星状细胞增殖作用研究*

doi:10.3969/j.issn.1672-5069.2016.02.006

Abstract

Abstract: Objective To invastigate the anti-proliferating and apoptotic effect of LY294002 and 1,25-dihydroxyvitamin D3（1,25-（OH）2D3） on hepatic stellate （HSC-T6） cells in vitro. MethodsThe HSC-T6 cells were divided into five groups, e.g. control, DMSO, 1,25-（OH）2D3,LY294002 and 1,25-（OH）2D3 plus LY294002. The inhibitory effects were detected by MTT assay; The cell morphology was observed under microscopy; The apoptosis was detected by FCM, and the expression of Ser473,AKT and caspase-3 protein were assayed by Western blotting.Results The inhibitory rate in 1,25-（OH）2D3 plus LY294002 group was 87.5%,much higher than 50.3% in 1,25-（OH）2D3 or 40.3% in LY294002 group （P<0.05） after 48 h intervention;the apoptotic rate in 1,25-（OH）2D3 plus LY294002 group was 92.12%,much higher than 71.0% in 1,25-(OH）2D3 or 34.0% in LY294002-intervented group（P<0.05）;the ratio of Bax/Bcl-2 increased (P<0.05）,and the expression of caspase-3 also increased obviously in 1,25-（OH）2D3 plus LY294002 group(P<0.05）.ConclusionLY294002 has an anti-fibrotic effect with the assistance of 1,25-（OH）2D3 on T6 cells in vitro.

Key words: T6 cells, LY294002, 1, 25-dihydroxyvitamin D3, Cell apoptosis, PI3 K /Akt signal pathway

Wang Lei, Li Xiaotian, Zhang Li, et al. Inhibitory and apoptotic effect of LY 294002in combination with 1,25-dihydroxyvitamin D3 on HSC T6 cells in vitro[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2016, 19(2): 147-150.

References

[1] O’Kelly J,Uskokovic M,Lemp N,et al. Novel gemini-vitamin D 3 analog inhibits tumor cell growth and modulates the Akt/mTOR signaling pathway. J Steroid Biochem Mol Biol, 2006,100:107-116.
[2] Coelho RP,Yuelling LM,Fuss B,et al. Neurotrophin-3 targets the translational initiation machinery in oligodendrocytes. Glia, 2009,57:1754-1764.
[3] Conforti F,Wang Y,Rodriguez JA,et al. Molecular pathways: Anticancer activity by inhibition of nucleocytoplasmic shuttling. Clin Cancer Res,2015,[ahead of print].
[4] Yin X,Ren M,Jiang H,et al. Downregulated AEG-1 together with inhibited PI3K/Akt pathway is associated with reduced viability of motor neurons in an ALS model. Mol Cell Neurosci,2015,68:303-313.
[5] Newman R,Turner M. The Role of p110delta in the development and activation of B lymphocytes. Adv Exp Med Biol, 2015,850:119-135.
[6] Khadem F,Gao X,Mou Z,et al. Hepatic stellate cells regulate liver immunity to visceral leishmaniasis through p110delta-dependent induction and expansion of Tregs in mice. Hepatology,2015,[ahead of print].
[7] Reif S,Lang A,Lindquist JN,et al. The role of focal adhesion kinase-phosphatidylinositol 3-kinase-akt signaling in hepatic stellate cell proliferation and type I collagen expression. J Biol Chem,2003,278:8083-8090.
[8] Liu PT,Stenger S,Tang DH,et al. Cutting edge:Vitamin D-mediated human antimicrobial activity against mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol,2007,179:2060-2063.
[9] 李艳芳,唐夕岚,凌文华. 1,25-二羟基维生素 D3 对小鼠非酒精性脂肪肝性肝纤维化进程的抑制作用. 世界华人消化杂志,2012,20:3191-3196.
[10] 邓文升,顾磊,周鸿,等. 1,25（OH） 2D3抑制肝纤维化大鼠肝组织 TGF-β1和 α-SMA 表达的研究. 肝胆胰外科杂志, 2015,27:214-218.
[11] Abramovitch S, Dahan-Bachar L,Sharvit E,et al. Vitamin D inhibits proliferation and profibrotic marker expression in hepatic stellate cells and decreases thioacetamide-induced liver fibrosis in rats. Gut,2011,60:1728-1737.
[12] 张金平,陈建平,张春江,等. 活性维生素 D3 在雷帕霉素预处理系膜细胞增殖与凋亡中的作用. 实用医学杂志,2014,30: 2363-2366.
[13] 任嫱,李睿,赵强,等. LY294002 在外源性 H2S 预处理肝纤维化大鼠肝星状细胞增殖和凋亡中的作用. 胃肠病学和肝病学杂志,2013,22:804-807.
[14] Gaca MD,Pickering JA,Arthur MJ,et al. Human and rat hepatic stellate cells produce stem cell factor:a possible mechanism for mast cell recruitment in liver fibrosis. J Hepatol,1999,30: 850-858.
[15] Wang J,Chu ES,Chen HY,et al. microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway. Oncotarget,2015,6:7325-7338.
[16] Novo E,Marra F,Zamara E,et al. Overexpression of Bcl-2 by activated human hepatic stellate cells: resistance to apoptosis as a mechanism of progressive hepatic fibrogenesis in humans. Gut,2006,55:1174-1182.
[17] Sancho-Bru P,Juez E,Moreno M,et al. Hepatocarcinoma cells stimulate the growth,migration and expression of pro-angiogenic genes in human hepatic stellate cells. Liver Int,2010,30:31-41.
[18] Zou CG,Gao SY,Zhao YS,et al. Homocysteine enhances cell proliferation in hepatic myofibroblastic stellate cells. J Mol Med,2009,87:75-84.
[19] Park SJ,Sohn HY,Yoon J,et al. Down-regulation of FoxO-dependent c-FLIP expression mediates TRAIL-induced apoptosis in activated hepatic stellate cells. Cell Signal,2009,21:1495-1503.

Inhibitory and apoptotic effect of LY 294002in combination with 1,25-dihydroxyvitamin D3 on HSC T6 cells in vitro

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