血管内皮生长因子C上调电压门控钠通道Nav1.6表达促进宫颈癌细胞的侵袭  

Vascular endothelial growth factor-C promotes the invasion of cervical cancer cells via up-regulating the expression of voltage-gated sodium channel subtype Nav1.6

作　　者：潘惠艳[1] 赵群[2] 詹阳[3] 赵丽红[1] 张卫华[1] 吴玉梅[2] 

机构地区：[1]首都医科大学附属北京妇产医院中心实验室,北京100026 [2]首都医科大学附属北京妇产医院妇瘤科,北京100026 [3]首都医科大学附属北京妇产医院病理科,北京100026

出　　处：《肿瘤》2012年第5期313-319,共7页Tumor

基　　金：教育部留学回国人员科研启动基金[编号:教外司留(2009)1590号];北京市自然科学基金(面上项目)(编号:7112052)

摘　　要：目的:探讨血管内皮生长因子C(vascular endothelial growth factor-C,VEGF-C)促进宫颈癌ME180细胞的侵袭和转移是否涉及电压门控钠通道(voltage-gated sodium channels,VGSCs)Nav1.6亚型的表达及其他可能的信号转导分子。方法:应用RT-PCR和免疫荧光定位的方法分别检测VEGF-C受体3(亦称Flt-4)和Nav1.6mRNA及其蛋白在ME180细胞中的表达和定位,Transwell法检测VEGF-C和Nav1.6对细胞侵袭的作用,实时荧光定量-PCR和蛋白质印迹法检测VEGF-C对Nav1.6mRNA和蛋白表达的影响及信号转导分子p38丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)在其中的作用。结果:ME180细胞表达Flt-4和Nav1.6mRNA,Flt-4和Nav1.6蛋白主要定位于细胞膜。50和100ng/L VEGF-C可分别增加细胞的侵袭指数[(27.2±5.2)%和(49.1±6.1)%],与对照组比较差异有统计学意义(P<0.05);VGSC抑制剂TTX(tetrodotoxin)可有效阻断VEGF-C促进的细胞侵袭作用(P<0.05)。VEGF-C可上调ME180细胞Nav1.6mRNA和蛋白的表达水平(P<0.05)。p38MAPK抑制剂PD169316可抑制VEGF-C促进的Nav1.6mRNA和蛋白的表达水平及细胞侵袭作用。结论:VEGF-C通过上调VGSC Nav1.6亚型的表达促进宫颈癌ME180细胞侵袭,而且p38MAPK参与了VEGF-C诱导的Nav1.6表达和细胞侵袭。Objective：To investigate whether vascular endothelial growth factor（VEGF）-C promotes the invasion and metastasis of cervical cancer cells via up-regulating the expression of voltage-gated sodium channel（VGSC） subtype Nav1.6 and other possible molecules in signaling transduction.Methods：The expressions of VEGF-C receptor 3（Flt-4） and Nav1.6 mRNAs and the localization of these proteins in ME180 cells were detected by RT-PCR and immunofluorescence,respectively.The effects of VEGF-C and Nav1.6 on the invasion of ME180 cells were examined by Transwell assay.The effects of VEGF-C on the expression levels of Nav1.6 mRNA and protein as well as the function of signaling transduction molecular p38 mitogen-activated protein kinase（MAPK） in ME180 cells were measured by real-time fluorogenic quantitative-PCR and Western blotting.Results：The ME180 cells expressed Flt-4 and Nav1.6 mRNAs which located on plasma membrane.As compared with the control,VEGF-C（50 and 100 ng/L） increased invasive ability of ME180 cells by（27.2±5.2）% and（49.1±6.1）%,respectively（P〈0.05）.The invasive ability of ME180 cells induced by VEGF-C was suppressed by TTX（tetrodotoxin）（P〈0.05）.The expression levels of Nav1.6 mRNA and protein were up-regulated by VEGF-C treatment（P〈0.05）,but these effects and the invasive ability of ME180 cells could be inhibited by PD169316,an inhibitor of p38 MAPK.Conclusion：VEGF-C promotes the invasion of cervical cancer ME180 cells via up-regulating the expression of Nav1.6,and p38 MAPK also play a role in the expression of Nav1.6 and the invasion of cervical cancer cells induced by VEGF-C.

关 键 词：宫颈肿瘤 血管内皮生长因子C 肿瘤侵润 电压门控钠离子通道 

分 类 号：R737.33[医药卫生—肿瘤]