芝麻酚对肺腺癌细胞侵袭能力的影响及机制研究  

Effects of sesamol on the invasive capacity of lung adenocarcinoma cells and its mechanism

作　　者：宁士龙 马宵 金惠仙 NING Shilong;MA Xiao;JIN Huixian(Department of Clinical Nutrition,Affiliated Jinhua Hospital,Zhejiang University School of Medicine,Jinhua 321000,China Corresponding;不详)

机构地区：[1]浙江大学医学院附属金华医院临床营养科,321000 [2]金华市妇幼保健院预防保健科

出　　处：《浙江医学》2025年第3期228-234,I0003,共8页Zhejiang Medical Journal

基　　金：国家自然科学基金项目(82204013);浙江省自然科学基金项目(LQ20H260010)。

摘　　要：目的探究芝麻酚对肺腺癌细胞侵袭能力的影响及酪氨酸蛋白激酶2(JAK2)/信号传导与转录激活因子3(STAT3)通路在其中的作用。方法采用噻唑蓝实验和预铺基质胶的细胞侵袭实验分别检测不同浓度芝麻酚处理后肺腺癌细胞系A549和SPC-A-1细胞活性和侵袭能力,实时荧光定量聚合酶链反应法检测细胞基质金属蛋白酶(MMP)-2、MMP-9、STAT3mRNA表达水平,蛋白质印迹法检测细胞MMP-2、MMP-9、STAT3、磷酸化STAT3(p-STAT3)、JAK2、磷酸化JAK2(p-JAK2)蛋白表达水平,明胶酶谱实验检测细胞MMP-2和MMP-9活性,脂质体Lipofectamine 2000转染法敲减细胞内STAT3后继续培养并检测MMP-2、MMP-9和STAT3 mRNA和蛋白表达水平,免疫荧光实验检测STAT3的定位。结果芝麻酚在不影响细胞活性的前提下,显著抑制肺腺癌细胞的侵袭能力。芝麻酚可降低MMP-2和MMP-9的表达和活性,且显著下调JAK2和STAT3的磷酸化水平,同时诱导STAT3由细胞核转位至细胞质中。结论芝麻酚可通过下调JAK2/STAT3通路活性降低MMP-2和MMP-9的表达及活性,进而抑制肺腺癌细胞的侵袭能力。Objective To investigate the effects of sesamol on the invasive capacity of lung adenocarcinoma cells and the role of janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway in it.Methods After treatment of lung adenocarcinoma cell lines A549 and SPC-A 1 by sesamol at different doses,methylthiazolyldiphenyl tetrazolium bromide and transwell assay with pre-coated matrigel were carried out to test the cellular viability and invasive capacity,respectively.Quantitative real-time polymerase chain reaction was applied to detect the mRNA levels of matrix metalloproteases(MMP)-2,MMP 9,and STAT3.Western blot assay was applied to test the protein levels of MMP 2,MMP 9,STAT3,phosphorylated STAT3(p-STAT3),JAK2 and phosphorylated JAK2(p-JAK2)in cells.Gelatin zymography was used to examine the activity of MMP 2 and MMP 9.After knockdown of STAT3 expression in lung adenocarcinoma cells with Lipofectamine 2000,the mRNA and protein levels of MMP 2,MMP 9 and STAT3 were examined.Immunofluorescence assay was performed to test the location of STAT3.Results Sesamol could effectively attenuate the invasive potential of lung adenocarcinoma cells without any influence on the cells'viability.In addition,sesamol treatment could significantly down-regulate the activity and expression of both MMP-2 and MMP-9.Furthermore,sesamol exposure inhibited JAK2/STAT3 pathway,characterized by declined phosphorylation of JAK2 and STAT3 as well as the translocation of STAT3 from nucleus to cytoplasm.Conclusion Sesamol reduces the activity and expression of both MMP-2 and MMP-9 via inhibition of JAK2/STAT3 pathway activity,leading to the down-regulation of lung adenocarcinoma cells'invasive capacity eventually.

关 键 词：芝麻酚 肺腺癌 酪氨酸蛋白激酶2/信号传导与转录激活因子3通路 侵袭 

分 类 号：R73[医药卫生—肿瘤]