西达本胺对胃癌SGC-7901细胞增殖、凋亡及Notch1、Sirt1基因表达的影响研究-东南大学学报医学版

西达本胺对胃癌SGC-7901细胞增殖、凋亡及Notch1、Sirt1基因表达的影响研究

单位：1. 东南大学附属中大医院肿瘤中心, 江苏南京 210009;
2. 东南大学环境医学工程教育部重点实验室, 江苏南京 210009

分类号：R965

出版年·卷·期（页码）：2012·31·第三期（273-276）

摘要：

目的:通过研究组蛋白去乙酰化酶抑制剂西达本胺对Notch1、Sirt1基因表达的影响来探讨其对胃癌细胞株SGC-7901的体外抗增殖作用。方法:采用MTT法观察不同浓度西达本胺对SGC-7901细胞增殖抑制作用,流式细胞仪(FCM)检测细胞凋亡率,RT-PCR检测Sirt1基因表达情况,蛋白质印迹法检测Notch1蛋白表达情况。结果:西达本胺在体外可抑制胃癌细胞SGC-7901增殖,呈浓度、时间依赖性;其可促进细胞凋亡,减少Sirt1基因的表达,下调Notch1蛋白的表达。结论:西达本胺可通过抑制Sirt1基因表达、下调Notch1蛋白的表达来抑制细胞增殖、促进细胞凋亡而发挥体外抗胃癌作用。

Objective: To investigate the influence of chidamide, a histone deacetylase inhibitor(HDACi), on the proliferation inhibition and apoptosis effects to the human gastric carcinoma cell lines SGC-7901 and to explore the related mechanism of Notch1, Sirt1. Methods: SGC-7901 cells were incubated with chidamide at various concentrations and times. Cell growth inhibition was assessed by MTT.Cell apoptosis was analyzed by flow cytomerty(FCM). The expression of Sirt1 mRNA were determined by RT-PCR, the protein levels of Notch1 were determined by Western blotting. Results: The proliferation of SGC-7901 cell was significantly inhibited and the apoptosis of SGC-7901 cell was promoted by chidamide(P<0.05). The expression of Sirt1 mRNA and the protein levels of Notch1 were reduced by chidamide. Conclusion: Chidamide can promote apoptosis and inhibit proliferation by down-regulation of Sirt1 and Notch1 expression in gastric carcinoma cells.

参考文献：

[1] RAHMAN S,ISLAM R.Mammalian Sirt1:insights on its biological functions[J].Cell Commun Signal,2011,9:11.
[2] IMAI S.The NAD world:a new systemic regulatory network for metabolism and aging—Sirt1,systemic NAD biosynthesis,and their importance[J].Cell Biochem Biophys,2009,53(2):65-74.
[3] KIM E J,KHO J H,KANG M R,et al.Active regulator of Sirt1 cooperates with Sirt1 and facilitates suppression of p53 activity[J].Mol Cell,2007,28(2):277-290.
[4] YEUNG F,HOBERG J E,RAMSEY C S,et al.Modulation of NF-kappaB-dependent transcription and cell survival by the Sirt1 deacetylase[J].EMBO J,2004,23(12):2369-2380.
[5] COHEN H Y,LAVU S,BITTERMAN K J,et al.Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis[J].Mol Cell,2004,13(5):627-638.
[6] BRUNET A,SWEENEY L B,STURGILL J F,et al.Stress-dependent regulation of FOXO transcription factors by the Sirt1 deacetylase[J].Science,2004,303(5666):2011-2015.
[7] FIRESTEIN R,BLANDER G,MICHAN S,et al.The Sirt1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth[J].PLoS ONE,2008,3(4):e2020.
[8] KOPAN R,LLAGAN M X.The canonical Notch signaling pathway:unfolding the activation mechanism[J].Cell,2009,137(2):216-233.
[9] LEONG K G,KARSAN A.Recent insights into the role of Notch signaling in tumorigenesis[J].Blood,2006,107(6):2223-2233.
[10] YOON H A,NOH M H,KIM B G,et al.Clinicopathological significance of altered Notch signaling in extrahepatic cholangiocarcinoma and gallbladder carcinoma[J].World J Gastroenterol,2011,17(35):4023-4030.
[11] 范任华,陈平圣,赵迪,等.失调的Notch信号与癌基因ras共同促进肝细胞转化与增殖[J].东南大学学报:医学版,2011,30(4):568-572.

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