瘦素通过抑制ACSL5促进乳腺癌细胞MCF-7的迁移和侵袭  

Leptin promotes breast cancer cell MCF-7 migration and invasion through inhibiting ACSL5

作　　者：曾涛 魏兰[1,2] 徐永柱[2] 杨诗雨 孙浩力 党婷婷 游毅青 唐加峰 张彦 ZENG Tao;WEI Lan;XU Yong-zhu;YANG Shi-yu;SUN Hao-li;DANG Ting-ting;YOU Yi-qing;TANG Jia-feng;ZHANG Yan(Key Laboratory of Clinical Laboratory Diagnosis,Ministry of Education,College of Laboratory Medicine,Chongqing Medical University,Chongqing 400016,China;Chongqing Blood Center,Chongqing 400015,China)

机构地区：[1]重庆医科大学检验医学院临床检验诊断学教育部重点实验室,重庆400016 [2]重庆市血液中心,重庆400015

出　　处：《中国药理学通报》2025年第4期654-660,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No.81974449);重庆市自然科学基金项目(No.CSTB2022NSCQ-MSX1076)。

摘　　要：目的研究拟探讨瘦素(leptin)对长链脂酰辅酶A家族成员长链脂酰辅A合成酶5(acyl-CoA synthetase long chain family member 5,ACSL5)的调控作用及机制,并探究其对乳腺癌细胞迁移和侵袭的影响。方法免疫荧光实验检测瘦素受体的表达;划痕愈合实验和Transwell实验检测细胞迁移、侵袭能力;采用PCR芯片数据分析瘦素下游靶基因,生物信息学方法分析ACSL5在乳腺癌中的表达、与患者分期及预后关系;RT-qPCR检测不同浓度瘦素处理后ACSL5的表达;慢病毒转染构建过表达ACSL5稳转株;Western blot检测上皮-间质转化(epithelial-mesenchymal transition,EMT)相关蛋白表达及AMPK-α、p-AMPK-α的表达。结果瘦素促进MCF-7细胞体外迁移和侵袭及EMT;ACSL5是瘦素下游靶基因,在乳腺癌中显著低表达且与患者预后相关;瘦素通过其受体OBR下调ACSL5的表达;瘦素激活AMPK通路下调ACSL5促进乳腺癌MCF-7细胞迁移和侵袭及EMT。结论瘦素可能通过激活AMPK通路下调ACSL5,增强乳腺癌细胞的迁移和侵袭能力并促进其EMT进程,从而促进乳腺癌恶性进展。Aim To explore the possible regulatory effect of leptin on acyl-CoA synthetase long chain family member ACSL5 and their effect on migration and invasion of breast cancer cell,and to explore the underlying mechanism.Methods The expression of leptin receptor was detected by immunofluorescence assay.The migration and invasion ability of MCF-7 cells were detected by wound healing assay and Transwell assay respectively.The downstream target gene of leptin was analyzed by PCR microarray data.The expression of ACSL5 in breast cancer and its correlation with the staging and prognosis of breast cancer patients were assessed uing bioinformatics methods.The expression of ACSL5 in MCF-7 cells treated with different concentrations of leptin was detected using real time fluorescence quantitative polymerase chain reaction(RT-qPCR).Overexpressing ACSL5 was constructed by lentiviral transfection;the expressions of EMT related proteins,AMPK-αand p-AMPK-αwere detected by Western blot.Results Leptin promoted breast cancer cell migration and invasion and EMT.ACSL5 was significantly low expressed in breast cancer and related to prognosis.Leptin downregulated the expression of ACSL5 through OBR.Leptin activated AMPK pathway to downregulate ACSL5 and promote migration,invasion and EMT of breast cancer cells.Conclusions Leptin may promote the migration,invasion and EMT of breast cancer by downregulating ACSL5 through activating AMPK pathway.

关 键 词：乳腺癌 瘦素 ACSL5 迁移 侵袭 上皮-间质转化 

分 类 号：R347[医药卫生—基础医学] R392.11R394.2R737.9R977.1