摘要
目的探究白术内酯Ⅰ在胃癌细胞中抑制输出蛋白T(XPOT)的作用和机制。方法探究XPOT在胃癌组织中的表达情况。自安徽中医药大学第二附属医院脾胃科病例随访系统中随机调出具有完整临床病理及随访资料的胃癌病例105例,并获取对应的肿瘤组织和癌旁组织。应用免疫组化、qPCR和Western blot技术检测上述标本中XPOT表达情况。使用GSEA分析TCGA、GEO数据库中胃癌患者基因表达数据。通过多种细胞实验检测癌细胞的增殖、迁移、侵袭能力。并检测XPOT、SKP2、CyclinA、P27的mRNA的蛋白表达水平。结果生物信息学结果及临床样本均证实,XPOT在胃癌组织中表达高,提示不良预后;体外研究发现:AT-1可抑制胃癌细胞的增殖、侵袭能力;XPOT下调可抑制胃癌细胞的增殖、侵袭能力;AT-1可下调XPOT表达,继而对SKP2、P27、CyclinA进行调控,即通过调控XPOT途径,抑制胃癌细胞的增殖和侵袭。结论胃癌组织中XPOT过表达可提示患者预后不良。白术内酯Ⅰ可下调XPOT调控泛素化-蛋白酶体途径抑制胃癌细胞的增殖及侵袭。
Objective This study aimed to investigate the role and mechanism of atractylenolide I in inhibiting XPOT proliferation and invasion in gastric cancer cells.Methods This study included exploration of XPOT expression in gastric cancer tissues,analysis of gene expression data from GC patients in TCGA and GEO databases,as well as various cellular assays to detect the ability of cancer cells to proliferate,migrate,and invade.Protein expression levels of XPOT,SKP2,CyclinA,and P27 mRNA were also detected by qPCR and Western Blot.Results Analysis confirmed that XPOT was highly expressed in gastric cancer tissues,indicating a poor prognosis.In vitro studies revealed that AT-1 inhibits the proliferation and invasion ability of GC cells;XPOT down-regulation also inhibits these abilities.Furthermore,AT-1 down-regulates the expression of XPOT which then regulates SKP2,P27,and CyclinA-ultimately inhibiting the proliferation and invasion of gastric cancer cells through the regulation of the XPOT pathway.Conclusion The overexpression of XPOT in gastric cancer tissues can indicate a poor prognosis.Atractylenolide I down-regulates the XPOT-regulated ubiquitination-proteasome pathway to inhibit proliferation and invasion of gastric cancer cells.
作者
张艺
马芳琪
魏思媛
李学军
ZHANG Yi;MA Fangqi;WEI Siyuan;LI Xuejun(Department of Spleen and Stomack,the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine,Hefei 230061,China;不详)
出处
《实用医学杂志》
CAS
北大核心
2024年第14期1928-1934,共7页
The Journal of Practical Medicine
基金
安徽省科技惠民专项(编号:2022e07020023)
安徽省自然科学基金项目(编号:2008085MH265)
安徽省名中医及基层名中医工作室建设项目(编号:中发展[2020]10号)。
关键词
白术内酯Ⅰ
胃癌
输出蛋白T
泛素化-蛋白酶体途径
atractylodes macrocephala lactone I
gastric cancer
XPOT
ubiquitination proteasome pathway
