PCSK9调控前列腺癌细胞生物学功能和铁死亡敏感性的作用研究  

The role of PCSK9 in regulating the biological function and ferroptosis sensitivity of prostate cancer cells

作　　者：王诗淳 史明慧 王丹琦 习舒 崔金龙 刘姝言 袁帅 靳英辉 WANG Shichun;SHI Minghui;WANG Danqi;XI Shu;CUI Jinlong;LIU Shuyan;YUAN Shuai;JIN Yinghui(Center for Evidence-Based and Translational Medicine,Zhongnan Hospital of Wuhan University,Wuhan 430071,China)

机构地区：[1]武汉大学中南医院循证与转化医学中心,武汉430071

出　　处：《药物流行病学杂志》2025年第3期282-292,共11页Chinese Journal of Pharmacoepidemiology

基　　金：湖北省自然科学基金面上项目(2023AFB742)。

摘　　要：目的探讨前蛋白转化酶枯草溶菌素9(PCSK9)在前列腺癌(PCa)中的生物学功能及其对铁死亡敏感性的影响,以期为PCa的治疗提供新的思路。方法利用生物信息学分析PCSK9与PCa预后的关系,并利用RT-qPCR检测PCa细胞系中PCSK9的表达情况。利用siRNA构建干扰PCSK9的PCa细胞,通过CCK-8实验和Transwell实验分析PCSK9在体外对细胞增殖、迁移和侵袭能力的影响。利用癌症治疗反应门户(CTRP)分析PCSK9与铁死亡药物敏感性的相关性,并通过铁死亡诱导剂(RSL3)处理PCa细胞,检测细胞敲低PCSK9后对铁死亡诱导剂敏感性的变化。结果生物信息学分析显示,PCSK9低表达患者具有较长的癌症特异性生存期(P<0.05)。体外实验结果表明,敲低PCSK9的表达能显著抑制PCa细胞的增殖、迁移和侵袭能力(P<0.001)。此外,CTRP分析显示细胞对铁死亡诱导剂的敏感性与PCSK9的表达水平相关;PCSK9敲低细胞对铁死亡诱导剂RSL3展现出更高的敏感性。结论敲低PCSK9抑制PCa细胞的增殖、迁移和侵袭,并增加细胞对铁死亡诱导剂的敏感性,有望为PCa的治疗提供新的思路。Objective To investigate the biological function of the proprotein convertase subtilisin/kexin type 9(PCSK9)in prostate cancer(PCa)and its effect on ferroptosis sensitivity Methods Bioinformatics was used to analyze the relationship between the expression of PCSK9 and the prognosis of prostate cancer.The expression of PCSK9 in PCa cell lines were detected using RT-qPCR.PCa cells with PCSK9 knockdown were constructed using siRNA,and the The effect of PCSK9 on cell proliferation,migration,and invasion were detected using CCK-8 assays and Transwell assays.The Cancer Therapeutics Response Portal(CTRP)was employed to investigate the correlation between PCSK9 and ferroptosis drug sensitivity,and PCa cells with PCSK9 knockdown were treated with the ferroptosis inducer(RSL3)to detect the sensitivity to ferroptosis.Results Bioinformatics showed low expression of PCSK9 had longer disease specific survival(P<0.05).The results of the in vitro experiments showed that PCSK9 knockdown significantly inhibited the proliferation,migration,and invasion of PCa cells(P<0.001).Furthermore,CTRP analysis showed that cellular sensitivity to ferroptosis inducers correlated with the expression level of PCSK9.PCSK9 knockdown cells exhibited higher sensitivity to the ferroptosis inducer RSL3.Conclusion Knockdown of PCSK9 inhibits the proliferation,migration,and invasion of PCa cells,and increases the sensitivity of cells to ferroptosis inducers.PCSK9 may provide new insights for the treatment of PCa.

关 键 词：前列腺癌 前蛋白转化酶枯草溶菌素9 增殖 迁移 侵袭 铁死亡 

分 类 号：R737.25[医药卫生—肿瘤]