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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

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【作者】 程杨袁金聂妙玲康佳丽

【Author】 CHENG Yang;YUAN Jin;NIE Miao-ling;KANG Jia-li;Department of Gynecology and Obstetrics,the First People′s Hospital of Guangzhou;

【通讯作者】 康佳丽;

【机构】 广州市第一人民医院妇产科

【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。

【Abstract】 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.

【基金】 广东省医学科研基金(A2015058)
  • 【文献出处】 热带医学杂志 ,Journal of Tropical Medicine , 编辑部邮箱 ,2018年07期
  • 【分类号】R737.33
  • 【被引频次】9
  • 【下载频次】85
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