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白细胞介素-8通过调节ERK/MMP-9信号通路促进子宫颈癌细胞恶性行为机制的研究

Mechanism of Interleukin-8 Promoting Malignant Development of Cervical Cancer Cells by Regulating ERK/MMP-9 Signaling Pathway

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【作者】 叶珂帆周争立

【Author】 YE Kefan;ZHOU Zhengli;Department of Gynecology,The First People′s Hospital of Yunnan Province,Affiliated Hospital of Kunming University of Science and Technology;

【通讯作者】 周争立;

【机构】 云南省第一人民医院昆明理工大学附属医院妇科

【摘要】 目的:探讨白细胞介素-8(IL-8)对子宫颈癌细胞侵袭、迁移以及细胞外信号调节激酶(ERK)/基质金属蛋白酶-9(MMP-9)表达的作用机制。方法:培养子宫颈癌细胞系SiHa、Caski、HeLa、C33A以及人正常子宫颈上皮细胞系HcerEpic,利用四氮甲基偶氮唑蓝(MTT)、Transwell及细胞划痕实验分别检测IL-8敲降和ERK激活剂对细胞增殖、侵袭及迁移能力的影响,实时荧光定量PCR(qRT-PCR)和蛋白免疫印迹(Western blot)检测MMP-9、ERK、磷酸化ERK(p-ERK)、上皮钙黏蛋白(E-cadherin)、神经元钙黏蛋白(N-cadherin)、IL-8的mRNA及蛋白表达水平。结果:IL-8在子宫颈癌细胞系中高表达;敲降IL-8显著抑制子宫颈癌细胞的增殖、迁移及侵袭,同时E-cadherin表达上调,N-cadherin、MMP-9和ERK、p-ERK表达下调;此外,敲降IL-8与ERK激活剂共同处理逆转了IL-8敲降对子宫颈癌生物学功能的抑制作用。结论:IL-8通过激活ERK信号通路上调MMP-9促进子宫颈癌细胞的增殖、侵袭以及迁移能力。

【Abstract】 Objective:To explore the mechanism of Interleukin-8(IL-8) on invasion, migration and extracellular signal-regulated kinase(ERK)/Matrix metallo proteinase-9(MMP-9) expression of cervical cancer cells.Methods: Cervical cancer cell lines SiHa, Caski, HeLa, C33 A and human normal cervical epithelial cell line HcerEpic were cultured.The effects of IL-8 knockdown on cell proliferation, invasion and migration were detected by MTT,Transwell and cell scratch assay respectively.The mRNA and protein expression levels of MMP-9,ERK,p-ERK,EMT-related proteins(E-cadherin, N-cadherin) and IL-8 were detected by qRT-PCR and Western blot.Results:IL-8 was highly expressed in cervical cancer cell lines.Knockdown of IL-8 significantly inhibited the proliferation, migration and invasion of cervical cancer cells, while the expression of E-cadherin was up-regulated, N-cadherin, MMP-9,ERK,and p-ERK were down-regulated.In addition, co-processing of knockdown of IL-8 and ERK/activator showed inhibitory effect of reverse transcription of IL-8 knockdown on the biological function of cervical cancer.Conclusions: IL-8 can promote the proliferation, invasion and migration of cervical cancer cells by activating ERK signaling pathway and upregulating MMP-9.

  • 【文献出处】 实用妇产科杂志 ,Journal of Practical Obstetrics and Gynecology , 编辑部邮箱 ,2022年09期
  • 【分类号】R737.33
  • 【下载频次】57
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