STAT3/iNOS信号对喉癌Hep-2细胞的增殖作用The proliferation effect of STAT3/iNOS signaling pathway in laryngeal cancer Hep-2 cell line
王莹;李文媛;赵晨辉;金在顺;刘艳翠;张洋;张晶;
摘要(Abstract):
目的观察信号转导及转录激活蛋白3(STAT3)/诱导型一氧化氮合酶(iNOS)信号通路对喉癌Hep-2细胞(Hep-2)的增殖作用,并探讨其作用机制。方法体外培养Hep-2细胞,STAT3慢病毒(2μL,1×1010病毒颗粒)和同剂量siRNA STAT3转染Hep-2细胞6 d后,细胞分为对照组、siRNA STAT3组和STAT3组。MTT法检测各组Hep-2细胞增殖情况。实时荧光定量PCR检测检测各组细胞STAT3、iNOS及血管内皮因子C(VEGF-C)mRNA相对表达。结果镜下观察STAT3组Hep-2细胞数量显著高于对照组和siRNA STAT3组,MTT法显示STAT3组Hep-2细胞在6 d增殖显著高于对照组和siRNA STAT3组(P<0.05),实时荧光定量PCR结果表明STAT3转染组STAT3、iNOS和VEGF-C mRNA表达显著高于对照组和siRNA STAT3组(P<0.05),而对照组和siRNA STAT3组STAT3、iNOS和VEGF-C蛋白表达未见显著差异(P﹥0.05)。STAT3与iNOS及VEGF-C mRNA表达显著正相关(P<0.05)。结论 STAT3/iNOS信号通路能够通过上调VEGF-C表达促进喉癌Hep-2细胞增殖,STAT3/iNOS信号通路可成为治疗喉癌新的靶点。
关键词(KeyWords): 喉癌Hep-2细胞;转录活化因子3;诱导型一氧化氮合酶;增殖
基金项目(Foundation): 牡丹江市科学技术计划项目(Z2014s035);; 牡丹江医学院科学技术研究项目(2s201331)
作者(Authors): 王莹;李文媛;赵晨辉;金在顺;刘艳翠;张洋;张晶;
DOI: 10.13799/j.cnki.mdjyxyxb.2016.06.004
参考文献(References):
- [1]CHONG H C,CHAN J S,GOH C Q,et al.Angiopoietin-like 4stimulates STAT3-mediated iNOS expression and enhances angiogenesis to accelerate wound healing in diabetic mice[J].Mol Ther,2014,22(9):1593-1604.
- [2]BANERJEE K,RESAT H.Constitutive activation of STAT3 in breast cancer cells:A review[J].Int J Cancer,2016,138(11):2570-2578.
- [3]HUANG K,LI LA,MENG Y G,et al.Arctigenin promotes apoptosis in ovarian cancer cells via the iNOS/NO/STAT3/survivin signalling[J].Basic Clin Pharmacol Toxicol,2014,115(6):507-511.
- [4]LIU J,MAO Y,ZHANG D,et al.MiR-143 inhibits tumor cell proliferation and invasion by targeting STAT3 in esophageal squamous cell carcinoma[J].Cancer Lett,2016,373(1):97-108.
- [5]王莹,李文媛,梁金花,等.iNOS和VEGF-C的表达与喉癌组织淋巴管生成及预后关系[J].肿瘤学杂志,2012,5(2):114-117.
- [6]WARD M C,CUNNINGHAM A M.Developmental expression of vascular endothelial growth factor receptor 3 and vascular endothelial growth factor C in forebrain[J].Neuroscience,2015,10(303):544-557.
- [7]YU Y,LI M,SU N,et al.Honokiol protects against renal ischemia/reperfusion injury via the suppressionof oxidative stress,iNOS,inflammation and STAT3 in rats[J].Mol Med Rep,2016,13(2):1353-1360.
- [8]PRAUSE M,BERCHTOLD L A,URIZAR A I,et al.TRAF2 mediates JNK and STAT3 activation in response to IL-1βand IFNγand facilitates apoptotic death of insulin-producingβ-cells[J].Mol Cell Endocrinol,2016,15(420):24-36.
- [9]KALIYAPERUMAL K,SHARMA A K,MCDONALD D G,et al.S-Nitrosoglutathione-mediated STAT3 regulation in efficacy of radiotherapy and cisplatin therapy in head and neck squamous cell carcinoma[J].Redox Biol,2015,6(2):41-50.
- [10]HUANG K,LI L A,MENG Y G,et al.Arctigenin promotes apoptosis in ovarian cancer cells via the iNOS/NO/STAT3/survivin signaling[J].Basic Clin Pharmacol Toxicol,2014,115(6):507-511.
- [11]KIM J A,YUN H M,JIN P,et al.Inhibitory effect of a 2,4-bis(4-hydroxyphenyl)-2-butenal diacetate on neuro-inflammatory reactions via inhibition of STAT1 and STAT3 activationin cultured astrocytes and microglial BV-2 cells[J].Neuropharmacology,2014,4(79):476-487.
- [12]ZENG K W,WANG S,DONG X,et al.Sesquiterpene dimer(DSF-52)from Artemisia argyi inhibits microglia-mediated neuroinflammation via suppression of NF-κB,JNK/p38 MAPKs and Jak2/Stat3 signaling pathways[J].Phytomedicine,2014,21(3):298-306.
- [13]WARD M C,CUNNINGHAM A M.Developmental expression of vascular endothelial growth factor receptor 3 and vascular endothelial growth factor C in forebrain[J].Neuroscience,2015,10(303):544-557.