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作 者:康苧心[1] 胡国华[1] 吴蔚[1] 蒋建国[1] 杨旋[1]
机构地区:[1]重庆医科大学附属第一医院耳鼻咽喉科,重庆400016
出 处:《临床耳鼻咽喉头颈外科杂志》2011年第9期419-422,共4页Journal of Clinical Otorhinolaryngology Head And Neck Surgery
摘 要:目的:探讨核因子κB(NF-κB)与喉癌循环肿瘤细胞(CTC)发生之间的相关性,并观察NFκ-B抑制剂PDTC对CTC的影响及可能机制。方法:裸鼠皮下接种喉癌Hep-2细胞,建立喉癌裸鼠模型。将60只裸鼠随机分为实验组(PDTC预处理组)、对照组(生理盐水组)及空白组(不接种喉癌细胞),每组各20只。肿瘤接种成功8周后处死裸鼠,采用RT-PCR法,以CK19mRNA为标记物检测各组中CTC的表达;取出肿瘤组织,测定其体积,免疫组织化学方法观察喉癌组织NF-κB的表达及激活情况,实时荧光定量PCR检测各组喉癌组织中血管内皮生长因子-C和基质金属蛋白酶-9 mRNA的表达。结果:CTC发生与NF-κB的表达率无明显关联,在CTC表达阳性的喉癌组织中,NFκ-B阳性率为90%,而在CTC表达阴性的喉癌组织中,NF-κB阳性率为56.7%(P>0.05),但其与NF-κB的活性有关;PDTC可抑制NF-κB的激活,减少喉癌裸鼠模型中CTC的发生率,PDTC组CTC阳性率为5%,明显低于对照组CTC的阳性率45%(P<0.01)。结论:PDTC可减少喉癌裸鼠模型中CTC的发生率,其作用可能得益于PDTC降低了喉癌发生转移的能力,其机制可能为PDTC通过抑制NF-κB活性而使血管内皮生长因子-C和基质金属蛋白酶-9表达下调,减少肿瘤组织新生血管形成及降低喉癌侵袭力有关。Objective:To investigate the correlation of the nuclear factor(NF-κB) and laryngocarcinoma circulating tumor cells(CTC),observe nuclear factor inhibitor PDTC on laryngeal cancer CTC and its possible mechanism.Method:In order to establish of laryngocarcinoma nude mice model,The nude mice inoculated with laryngocarcinoma Hep-2 cells.To 50 nude mice were randomly divided into experimental group(PDTC pretreatment group),the control group(saline group),and Sham group(not inoculated carcinoma cells),tumor inoculated mice were labeled with CK-19 CTC markers,and sacrificed after 8 weeks,then RT-PCR detect CK-19mRNA expression in peripheral blood as to understand the expression of laryngocarcinoma CTC;removed tumor to determine its size,immunohistochemical expression of NF-κB in laryngocarcinoma,real-time fluorescence Quantitative PCR detection of laryngocarcinoma VEGF and MMP-9mRNA expression.Result:CTC occurrence and the expression of NF-κB was not obviously associated,expression in the CTC-positive laryngeal carcinoma,NF-κB-positive rate was 90%,while the expression of negative CTC laryngocarcinoma,NF-κB-positive rate was 56.7%(P 0.05),but connected with the activity of NF-κB;PDTC can inhibit NF-κB activation,reduce the incidence of CTC in laryngocarcinoma nude mice model,PDTC group CTC positive rate of 5%,significantly lower than the control group CTC positive rate of 45%(P0.01).Conclusion:PDTC can reduce the incidence of CTC in the laryngocarcinoma nude mouse model,its role may benefit from PDTC reduced the ability of laryngocarcinoma metastasis,which may be as PDTC inhibit NF-κB activity,thus make VEGF-C and the expression of MMP-9 down,reducing angiogenesis and reduce tumor invasion of the larynx.
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