PCSK9通过MAPK/ERK通路促进卵巢癌细胞体外增殖和侵袭的实验研究  

PCSK9 promotes proliferation and invasion of ovarian cancer cells in vitro through MAPK/ERK pathway

作　　者：吴敏敏 骆婕 廖凤儿 郑婷 范荻 郭琴 WU Minmin;LUO Jie;LIAO Fenger;ZHENG Ting;FAN Di;GUO Qin(Department of Obstetrics and Gynecology,The First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 510062,China)

机构地区：[1]广东药科大学附属第一医院妇产科,广东广州510062

出　　处：《中国病理生理杂志》2025年第3期444-452,共9页Chinese Journal of Pathophysiology

基　　金：广东省医学科学技术研究基金项目(No.A2021477)。

摘　　要：目的:探讨前蛋白转化酶枯草杆菌蛋白酶/可辛蛋白酶9型(proprotein convertase subtilisin/kexin type 9, PCSK9)在卵巢癌中的作用及机制。方法:比较卵巢癌标本与相应的癌旁组织中PCSK9的表达水平的差异,并同步检测其在卵巢癌细胞系中的表达情况。用shRNA敲减体外培养的卵巢癌细胞系中PCSK9的表达并通过Western blot进行证实。通过EdU、集落形成和Transwell实验分析敲减PCSK9对卵巢癌细胞增殖、迁移和侵袭的影响。用Western blot研究敲减PCSK9对MAPK/ERK信号通路的影响,并用MAPK/ERK信号通路激动剂以及PCSK9过表达质粒挽救实验验证MAPK/ERK信号通路参与PCSK9调控卵巢癌细胞的恶性生物学行为。结果:PCSK9在卵巢癌组织和细胞系中显著上调(P<0.01)。敲减PCSK9抑制了卵巢癌细胞的细胞增殖、迁移和侵袭(P<0.01)。Western blot结果显示,敲减PCSK9降低了MAPK/ERK信号通路关键分子的表达水平(P<0.01)。反向激活MAPK/ERK信号通路和回补PCSK9表达逆转了敲减PCSK9对卵巢癌细胞的抑制作用。结论:PCSK9通过激活MAPK/ERK信号通路途径促进卵巢癌细胞的增殖和侵袭。AIM:This study aims to investigate the role and mechanism of proprotein convertase subtilisin/kexin type 9(PCSK9)in ovarian cancer.METHODS:We compared the expression levels of PCSK9 between ovarian cancer specimens and their corresponding adjacent non-cancerous tissues,while also assessing its expression in various ovarian cancer cell lines.Using a shRNA strategy,we reduced the expression of PCSK9 in ovarian cancer cell lines cultured in vitro,with confirmation via Western blot.The effects of PCSK9 downregulation on the proliferation,migration,and invasion of ovarian cancer cells were evaluated through EdU,colony formation,and Transwell assays.Additionally,we analyzed the impact of PCSK9 down-regulation on the MAPK/ERK signaling pathway using Western blot analysis.RE-SULTS:PCSK9 was significantly upregulated in ovarian cancer tissues and cell lines(P<0.01).Downregulation of PC-SK9 resulted in a significant decrease in cell proliferation,migration,and invasion(P<0.01).Western blot analysis demonstrated that PCSK9 knockdown led to reduced expression levels of key molecules within the MAPK/ERK signaling pathway(P<0.01).CONCLUSION:PCSK9 promotes the proliferation and invasion of ovarian cancer cells by activating MAPK/ERK signaling pathway.

关 键 词：卵巢癌 PCSK9蛋白 生物标志物 MAPK/ERK信号通路 

分 类 号：R363[医药卫生—病理学] R737.31[医药卫生—基础医学] Q279[生物学—细胞生物学]