摘要
目的:探讨多能蛋白聚糖(VCAN)和基质金属蛋白酶9(MMP9)在肺腺癌(LUAD)侵袭与转移中的作用及其调控机制。方法:收集30例LUAD及配对癌旁组织,采用免疫组织化学(IHC)法检测VCAN和MMP9表达;另以人LUAD细胞NCIH1975和A549为模型,运用siRNA干扰和质粒过表达技术,结合挽救实验,采用CCK-8、划痕愈合实验及Transwell实验评估细胞增殖、迁移与侵袭能力,RT-qPCR及WB法检测基因和蛋白表达。结果:VCAN和MMP9在LUAD组织中的表达均显著高于癌旁组织(均P<0.001),且H-score随肿瘤分期的进展呈递增趋势(均P<0.01)。体外实验表明,si-VCAN显著降低VCAN和MMP9的mRNA及蛋白水平,抑制细胞活力、迁移和侵袭(均P<0.01);过表达MMP9则显著增强上述恶性表型(均P<0.001),并可被si-VCAN逆转(均P<0.01),而MMP9沉默对VCAN蛋白表达无显著影响(P > 0.05)。结论:VCAN通过上调MMP9表达促进LUAD细胞的增殖、迁移和侵袭,VCAN/MMP9轴可能成为LUAD治疗的潜在靶点。
Objective:To investigate the roles and regulatory mechanisms of versican(VCAN)and matrix metalloproteinase-9(MMP9)in the invasion and metastasis of lung adenocarcinoma(LUAD).Methods:Thirty LUAD specimens and their matched adjacent non-tumor tissues were collected.Immunohistochemistry(IHC)was performed to detect VCAN and MMP9 expressions.Human LUAD cell lines NCI-H1975 and A549 were employed as models.siRNA interference and plasmid overexpression,combined with rescue assays,were applied.Cell proliferation,migration,and invasion abilities were evaluated by CCK-8,scratch-healing assay,and Transwell assay,respectively.Gene and protein expression were detected by RT-qPCR and WB assay.Results:VCAN and MMP9 were significantly up-regulated in LUAD tissues compared with those in adjacent non-tumor tissues(both P<0.001),and their H-score increased progressively with advancing tumor stage(both P<0.01).In vitro experiments revealed that si-VCAN markedly reduced VCAN and MMP9 mRNA and protein levels and suppressed cell viability,migration,and invasion(all P<0.01),whereas MMP9 overexpression significantly promoted these malignant phenotypes(all P<0.001);these effects were reversed by si-VCAN(all P<0.01).MMP9 knockdown did not significantly affect VCAN protein levels(P>0.05).Conclusion:VCAN enhances the proliferation,migration,and invasion of LUAD cells by up-regulating MMP9.The VCAN/MMP9 axis may represent a potential therapeutic target for LUAD.
作者
黄炜祺
黄瑜
刘小婷
代丹
何翔
董健
HUANG Weiqi;HUANG Yu;LIU Xiaoting;DAI Dan;HE Xiang;DONG Jian(Department of Respiratory Medicine,Union Jiangbei Hospital,Huazhong University of Science and Technology,Wuhan 430000,Hubei,China;Department of Nephrology,Wuhan Third Hospital,Wuhan 430000,Hubei,China)
出处
《中国肿瘤生物治疗杂志》
北大核心
2025年第8期854-861,共8页
Chinese Journal of Cancer Biotherapy
基金
湖北省卫生健康委科研项目(No.WJ2023M148)
武汉市卫生科研基金(No.WZ22Q01)
华中科技大学协和江北医院自由创新预研基金(No.XHJBKXYJJJ-QNXM-06)。
关键词
多能蛋白聚糖
迁移
侵袭
肺腺癌
基质金属蛋白酶9
versican(VCAN)
migration
invasion
lung adenocarcinoma(LUAD)
matrix metalloproteinase-9(MMP9)
