VEGF-C激活ERK1/2上调Slug蛋白表达促进宫颈癌细胞侵袭  

VEGF-C activates ERK1/2 and up-regulates slug protein expression to promote cervical cancer invasion

作　　者：程杨[1] 袁金[1] 聂妙玲[1] 康佳丽[1] CHENG Yang;YUAN Jin;NIE Miao-ling;KANG Jia-li(Department of Gynecology and Obstetrics,the First People＇s Hospital of Guangzhou,Guangzhou,Guangdong 510180,China)

机构地区：[1]广州市第一人民医院妇产科,广东广州510180

出　　处：《热带医学杂志》2018年第7期846-849,868,共5页Journal of Tropical Medicine

基　　金：广东省医学科研基金(A2015058)

摘　　要：目的研究血管内皮生长因子C(VEGF-C)促子宫颈癌细胞侵袭能力的影响,探讨Slug在其中的作用及相关信号转导途径。方法体外培养宫颈癌细胞株Si Ha细胞,观察VEGF-C对ERK1/2磷酸化及Slug蛋白表达的影响;转染Slug si RNA后,采用transwell侵袭小室法观察其对宫颈癌细胞株增殖和侵袭的影响。结果 VEGF-C(100 ng/m L)处理Si Ha细胞12、24、48 h后,均能促进Slug蛋白表达,其表达幅度分别为(162.4±6.8)%、(202.8±9.4)%、(236.6±15.5)%,与对照组比较,差异均有统计学意义(P<0.05)。同时,VEGF-C处理后可促进ERK1/2蛋白磷酸化,表达幅度分别为(162.6±20.4)%、(197.8±25.6)%、(152.3±14.6)%,与对照组比较,差异均有统计学意义(P<0.05)。转染ERK1/2 si RNA可显著抑制VEGF-C促Slug表达的效应。Si Ha细胞转染特异性Slug si RNA 48 h后,VEGF-C促细胞侵袭的能力明显减弱。结论 VEGF-C可能通过激活ERK1/2,上调Slug蛋白表达,促进宫颈癌侵袭能力及其恶性进展。Objective To investigate the role of extrallular signal regulated protein kinase 1/2（ERK1/2）and Slug proteinin vascular endothelial growth factor C（VEGF-C）-enhanced cervical cancer metastasis.Methods Cervical cancer cell lineSi Ha cells were cultured and treated with VEGF-C to observe its effect on the phosphorylation or expression of ERK1/2 andslug.After transfected with specific slug si RNA,the invasion number of cultured cells were calculated by transwell chamberassay.Results Treatment with VEGF-C（100 ng/m L）for 12 h,24 h and 48 h could increase slug protein expression,withthe expression abundance of（162.4 ± 6.8）%（P〈0.05）,（202.8 ± 9.4）%（P〈0.01）,and（236.6 ± 15.5）%（P〈0.001）,respectively,when compared to control（100%）.Meanwhile,the same treatment with VEGF-C also increased ERK1/2 protein phosphorylation,with the expression abundance of（162.6 ± 20.4）%（P〈0.01）,（197.8 ± 25.6）%（P〈0.001）and（152.3±14.6）%（P〈0.01）,respectively.The transfection of ERK1/2 si RNA significantly impaired the VEGF-C effect onSIP1 expression.Finally,VEGF-C promoted Si Ha cell invasion,which was largely inhibited by the slug si RNA.Conclusion VEGF-C activated ERK1/2,thus increased slug expression and promotes cervical cancer cell invasion,whichmight contribute to cervical cancer malignant progression.

关 键 词：宫颈癌 血管内皮生长因子C SLUG 细胞外信号调节激酶1/2 

分 类 号：R737.33[医药卫生—肿瘤]