靶向抑制FOXC2对舌鳞癌细胞移植瘤血管形成的影响
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摘要
目的:研究靶向抑制叉头框C2(FOXC2)的表达对舌鳞癌细胞系Tca8113移植瘤血管形成的影响。方法:将舌癌Tca8113细胞系接种40只裸鼠皮下建立移植瘤模型,并随机分为空白对照组、空载体组、无关片段组、干扰质粒组。用脂质体法对空载体组、无关片段组、干扰质粒组进行瘤内及瘤周注射转染,RNA干扰抑制FOXC2的表达,处死裸鼠后取瘤体测量体质量及体积,免疫印迹法检测FOXC2蛋白表达,免疫组织化学法检测移植瘤微血管参数。结果:干扰质粒组的瘤体体积、体质量、FOXC2蛋白表达、微血管参数均小于其他各组(P<0.05)。结论:通过RNA干扰靶向抑制FOXC2的表达,能抑制舌鳞癌细胞移植瘤的血管形成。
Objective: To study the effects of targeting FOXC2 inhibition on the angiogenesis of tongue cancer cell xenografts.Methods: Tca8113 tongue caner cells were injected subcutaneously into the nude mice in the right underside backs to establish xenograft models,and mice were divided into non-transfected group,mock control group,control group transfected with scrambled sequence plasmid,and interference group transfected with FOXC2-shRNA expression plasmid. Then,liposome-mediated plasmid transfection was done in the latter 3 groups every 3 days. After mice were sacrificed,weight and size of xenografts were measured. Expression of FOXC2 protein was examined using western blot analysis. Microvessel parameters were detected using immunohistochemical staining. Results:Weight and size of xenografts,FOXC2 expression and microvessel parameters in interference group transfected with FOXC2-shRNA expression plasmids were less than the other three groups( P< 0.05). Conclusions: Targeting FOXC2 inhibition could suppress the angiogenesis of tongue cancer cell xenografts,suggesting that it may become a potential therapy for tongue squamous cell cancer.
Objective: To study the effects of targeting FOXC2 inhibition on the angiogenesis of tongue cancer cell xenografts.Methods: Tca8113 tongue caner cells were injected subcutaneously into the nude mice in the right underside backs to establish xenograft models,and mice were divided into non-transfected group,mock control group,control group transfected with scrambled sequence plasmid,and interference group transfected with FOXC2-shRNA expression plasmid. Then,liposome-mediated plasmid transfection was done in the latter 3 groups every 3 days. After mice were sacrificed,weight and size of xenografts were measured. Expression of FOXC2 protein was examined using western blot analysis. Microvessel parameters were detected using immunohistochemical staining. Results:Weight and size of xenografts,FOXC2 expression and microvessel parameters in interference group transfected with FOXC2-shRNA expression plasmids were less than the other three groups( P< 0.05). Conclusions: Targeting FOXC2 inhibition could suppress the angiogenesis of tongue cancer cell xenografts,suggesting that it may become a potential therapy for tongue squamous cell cancer.
引文
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[9]Sano H,Leboeuf JP,Novitskiy SV,et al.The Foxc2 transcription factor regulates tumor angiogenesis[J/OL].Biochem Biophys Res Commun,2010,392(2):201-206[2017-02-24].http://dx.doi.org/10.1016/j.bbrc.2010.01.015.
[10]Xouri G,Christian S.Origin and function of tumor stroma fibroblasts[J/OL].Semin Cell Dev Biol,2010,21(1):40-46[2017-02-24].http://dx.doi.org/10.1016/j.semcdb.2009.11.017.
[11]Li W,Fu X,Liu R,et al.FOXC2 often overexpressed in glioblastoma enhances proliferation and invasion in glioblastoma cells[J/OL].Oncol Res,2013,21(2):111-120[2017-02-24].http://dx.doi.org/10.3727/096504013X13814233062171.
[12]Ren YH,Liu KJ,Wang M,et al.De-SUMOylation of FOXC2 by SENP3 promotes the epithelial-mesenchymal transition in gastric cancer cells[J/OL].Oncotarget,2014,5(16):7096-7104[2017-02-24].http://dx.doi.org/10.18632/oncotarget.2197.
[13]贺路航,向橦,张艳玲,等.CD133+卵巢癌干细胞样细胞向血管内皮细胞分化的实验研究[J].第三军医大学学报,2014,36(5):413-416.
[14]李逸仙,孙保存,刘志勇,等.血管内皮诱导培养基促进结肠癌细胞向血管内皮细胞方向分化的研究[J].中国肿瘤临床,2014,41(10):620-623.
[15]姚金光,解继胜,李俊,等.舌癌单细胞培养建系与癌干细胞相关标志的检测[J].华西口腔医学杂志,2013,31(1):86-90.
[2]Golden D,Cantley LG.Casein kinase 2 prevents mesenchymal transformation by maintaining Foxc2 in the cytoplasm[J/OL].Oncogene,2016,34(36):4702-4712[2017-02-24].http://dx.doi.org/10.1038/onc.2014.395.
[3]Hollier BG,Tinnirello AA,Werden SJ,et al.FOXC2 links epithelial-mesenchymal transition and stem cell properties in breast cancer[J/OL].Cancer Res,2013,73(6):1981-1992[2017-02-24].http://dx.doi.org/10.1158/0008-5472.CAN-12-2962.
[4]Kume T.The Role of Fox C2 Transcription factor in tumor angiogenesis[J/OL].J Oncol,2012,2012:204593[2017-02-24].http://dx.doi.org/10.1155/2012/204593.
[5]Weidner N,Semple JP,Welch WR,et al.Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma[J].New Engl J Med,1991,324(1):1-8.
[6]Imayama N,Yamada S,Yanamoto S,et al.FOXC2 is associated with tumor proliferation and invasion potential in oral tongue squamous cell carcinoma[J/OL].Pathol Oncol Res,2015,21(3):783-791[2017-02-24].http://dx.doi.org/10.1007/s12253-014-9891-6.
[7]Nishida N,Mimori K,Yokobori T,et al.FOXC2 is a novel prognostic factor in human esophageal squamous cell carcinoma[J/OL].Ann Surg Oncol,2011,18(2):535-542[2017-02-24].http://www.springerlink.com/content/26406m3043v211n4/.DOI:10.1245/s10434-010-1274-y.
[8]Kume T.Foxc2 transcription factor:a newly described regulator of angiogenesis[J/OL].Trends Cardiovasc Med,2008,18(6):224-228[2017-02-24].http://www.sciencedirect.com/science/article/pii/S1050173808001266.DOI:10.1016/j.tcm.2008.11.003.
[9]Sano H,Leboeuf JP,Novitskiy SV,et al.The Foxc2 transcription factor regulates tumor angiogenesis[J/OL].Biochem Biophys Res Commun,2010,392(2):201-206[2017-02-24].http://dx.doi.org/10.1016/j.bbrc.2010.01.015.
[10]Xouri G,Christian S.Origin and function of tumor stroma fibroblasts[J/OL].Semin Cell Dev Biol,2010,21(1):40-46[2017-02-24].http://dx.doi.org/10.1016/j.semcdb.2009.11.017.
[11]Li W,Fu X,Liu R,et al.FOXC2 often overexpressed in glioblastoma enhances proliferation and invasion in glioblastoma cells[J/OL].Oncol Res,2013,21(2):111-120[2017-02-24].http://dx.doi.org/10.3727/096504013X13814233062171.
[12]Ren YH,Liu KJ,Wang M,et al.De-SUMOylation of FOXC2 by SENP3 promotes the epithelial-mesenchymal transition in gastric cancer cells[J/OL].Oncotarget,2014,5(16):7096-7104[2017-02-24].http://dx.doi.org/10.18632/oncotarget.2197.
[13]贺路航,向橦,张艳玲,等.CD133+卵巢癌干细胞样细胞向血管内皮细胞分化的实验研究[J].第三军医大学学报,2014,36(5):413-416.
[14]李逸仙,孙保存,刘志勇,等.血管内皮诱导培养基促进结肠癌细胞向血管内皮细胞方向分化的研究[J].中国肿瘤临床,2014,41(10):620-623.
[15]姚金光,解继胜,李俊,等.舌癌单细胞培养建系与癌干细胞相关标志的检测[J].华西口腔医学杂志,2013,31(1):86-90.