AMPK抑制剂抑制FASN影响宫颈癌细胞胆固醇代谢过程  

Inhibition of FASN by AMPK inhibitor affects the process of cholesterol metabolism in cervical cancer cells

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作  者:张慧慧 程翠 李艳 魏丽 王丽华 王亮亮 ZHANG Huihui;CHENG Cui;LI Yan;WEI Li;WANG Lihua;WANG Liangliang(Department of Gynecologic Oncology,The First Affiliated Hospital of Bengbu Medical University,Bengbu 233000,Anhui,China)

机构地区:[1]蚌埠医科大学第一附属医院妇瘤科,安徽蚌埠233000

出  处:《右江民族医学院学报》2024年第5期661-666,共6页Journal of Youjiang Medical University for Nationalities

基  金:蚌埠医科大学自然科学重点项目(2021byzd146)。

摘  要:目的探明AMPK抑制剂影响脂肪酸合成酶(FASN)调控宫颈癌细胞胆固醇代谢过程的分子机制。方法免疫组化检测FASN在宫颈癌中的表达,CCK-8、EdU、胆固醇检测沉默FASN后对宫颈癌增殖和胆固醇影响,IF检测各组脂筏和p-FAK的表达情况,Western Blot检测调控FASN后FASN、ERK1/2、p-ERK1/2、p-JUN和p-p38的表达。结果FASN在宫颈癌中过表达,高表达FASN与较差的预后直接相关。沉默FASN组的增殖、胆固醇和游离胆固醇水平下降,且脂筏表达下降。相较于NC组,si-FASN组中p-FAK的表达下降。相较于NC组,si-FASN组和MAK8722组(AMPK抑制剂)中FASN、p-ERK1/2、p-JUN和p-p38的表达下降。结论沉默FASN调控宫颈癌细胞胆固醇代谢和增殖过程,而加入AMPK抑制剂后抑制了FASN和AMPK信号轴的关键蛋白表达。Objective To explore the molecular mechanism through which AMPK inhibitor affects the regulation of fatty acid synthase(FASN)on cholesterol metabolism in cervical cancer cells.Methods The expression of FASN in cervical cancer was detected by immunohistochemistry.The effects of silenced FASN on proliferation and cholesterol of cervical cancer were detected by CCK-8,EdU and cholesterol detection.IF was used to detect the expression of lipid rafts and phosphorylated focal adhesion kinase(p-FAK)in various groups.Western Blot analysis was performed to evaluate the expression of FASN,ERK1/2,p-ERK1/2,p-JUN,and p-p38 after modulation of FASN.Results FASN was overexpressed in cervical cancer,and high FASN expression was directly associated with poor prognosis.The proliferation,cholesterol,and free cholesterol levels decreased in the FASN-silenced group,accompanied by reduced lipid raft expression.Compared with the negative control(NC)group,the expression of p-FAK was decreased in the si-FASN group.Additionally,the expressions of FASN,p-ERK1/2,p-JUN,and p-p38 were decreased in both the si-FASN group and the MAK8722 group(AMPK inhibitor)compared with the NC group.Conclusion Silencing of FASN regulates the cholesterol metabolism and proliferation in cervical cancer cells.Additionally,the addition of AMPK inhibitor further inhibits the expression of key proteins in the FASN and AMPK signaling axis.

关 键 词:脂肪酸合成酶 AMPK信号通路 胆固醇代谢 宫颈肿瘤 

分 类 号:R737.33[医药卫生—肿瘤]

 

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