吉非替尼对子宫内膜癌Ishikawa细胞增殖和凋亡的影响Effect of gefitinib on the proliferation and apoptosis to human endometrial cancer cell Ishikawa
云聪;赵焕焕;李利;
摘要(Abstract)：
目的:探讨EGFR酪氨酸激酶抑制剂吉非替尼(Gefitinib)对子宫内膜癌Ishikawa细胞增殖和凋亡的影响,并探讨其内在作用机制。方法:MTT法检测不同浓度吉非替尼作用后细胞的增殖抑制率。采用流式细胞术检测吉非替尼作用48h后的细胞凋亡率及细胞周期分布,并用倒置显微镜对细胞进行形态学观察。Western blot法检测不同浓度吉非替尼作用细胞48h后细胞内p-Akt、CyclinD1蛋白水平表达的变化。结果:吉非替尼能显著抑制Ishikawa细胞的增殖,促进细胞凋亡,且呈时间-剂量依赖性(P<0.05),并使细胞周期中G0/G1期比例升高(P<0.05),而对S期和G2/M期比例无明显影响(P>0.05)。吉非替尼作用48h后,Ishikawa细胞中p-Akt、CyclinD1蛋白表达随着吉非替尼浓度的增加逐渐下降(P<0.05)。结论:吉非替尼对人子宫内膜癌细胞Ishikawa的体外生长具有明显的抑制作用,并能诱导Ishikawa的凋亡,导致G0/G1期细胞阻滞,其分子机制可能与吉非替尼下调p-Akt蛋白及CyclinD1蛋白的表达有关。
关键词(KeyWords)： 吉非替尼;子宫内膜癌;Ishikawa细胞株;细胞周期;凋亡;p-Akt;CyclinD1
基金项目(Foundation):
作者(Authors): 云聪;赵焕焕;李利;
DOI: 10.13283/j.cnki.xdfckjz.2014.04.006
参考文献(References)：
- [1]Noro R,Gemma A,Kosaihira S,et al.Gefitinib(IRESSA)sensitive lung cancer cell lines show phosphorylation of Akt without ligand stimulation[J].BMC Cancer,2006,6:227
- [2]Cristofanilli M,Valero V,Mangalik A,et al.PhaseⅡ,randomized trial to compare anastrozole combined with gefitinib or placebo in postmenopausal women with hormone receptor-positive metastatic breast cancer[J].Clin Cancer Res,2010,16(6):1904-1914
- [3]朱秀敏.细胞凋亡的形态特征与分子机制研究进展[J].中国老年学杂志,2011,31(13)2595-2597
- [4]张雷英,傅芬.子宫内膜癌表皮生长因子受体及其靶向治疗的研究进展[J].实用医学杂志,2012,28(8):1371-1373
- [5]Gillet JP,Macadangdang B,Fathke RL.The development of gene therapy:from monogenic recessive disorders to complex diseases such as cancer[J].Methods Mol Biol,2009,542:5-54
- [6]Ciardiello F,Caputo R,Bianco R,et al.Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD1839(Iressa),an epidermal growth factor receptor selective tyrosine kinase inhibitor[J].Clin Cancer Res,2000,6(5):2053-2063
- [7]Hopfner M,Sutter AP,Huether A,et al.Targeting the epidermal growth factor receptor by gefitinib for treatment of hepatocellular carcinoma[J].J Hepatol,2004,41(6):1008-1016
- [8]Testa JR,Bellacosa A.AKT plays a central role in tumorigenesis[J].Proc Natl Acad Sci USA,2001,98(20):10983-10985
- [9]Dicholson KM,Anderson NG.The protein kinase B/Akt signaling pathy in human maliganancy[J].Cell Signal,2002,14(5):381-395
- [10]张琛,杨清,王玉.PIK3CB、Akt及p-Akt在子宫内膜癌中的表达及意义[J].中国医科大学学报,2012,41(6):544-546,549
- [11]李志伟,李彩虹,张智慧,等.子宫内膜癌中PTEN蛋白、P-AKT蛋白的表达意义[J].现代肿瘤医学,2013,21(3):633-635
- [12]Zhou P,Jiang W,Weghorst CM,et al.Overexpression of CyclinD1 enhances gene amplification[J].Cancer Res,1996,56(1):36-39
- [13]李永昊,肖玉周,汪万英,等.CyclinD1、CDK4、P16在骨肉瘤中的表达及临床意义[J].中华全科医学,2012,10(2):191-192,207
- [14]李启炯,宋军民,陆敏,等.CyclinD1在肝细胞癌中的表达及与肝细胞癌患者预后的关系[J].中华临床医师杂志,2012,6(2):356-360