叶酸修饰脂质体槲皮素经JAK2/STAT3信号通路介导的线粒体凋亡途径诱导三阴性乳腺癌细胞凋亡  

Folic Acid-Modified Liposome Quercetin Induces Apoptosis of Triple-Negative Breast Cancer Cells via Mitochondrial Apoptosis Mediated by JAK2/STAT3 Signaling Pathway

作　　者：陈凤霞 浦飞飞 CHEN Fengxia;PU Feifei(Department of Radiation and Medical Oncology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China;Hubei Provincial Clinical Research Center for Cancer,Wuhan 430071,China;Hubei Key Laboratory of Tumor Biological Behavior,Wuhan 430071,China;Department of Orthopedics,Wuhan Hospital of Traditional Chinese and Western Medicine(Wuhan No.1 Hospital),Wuhan 430022,China)

机构地区：[1]武汉大学中南医院肿瘤放化疗科,武汉430071 [2]湖北省肿瘤医学临床研究中心,武汉430071 [3]肿瘤生物学行为湖北省重点实验室,武汉430071 [4]武汉市中西医结合医院(武汉市第一医院)骨科,武汉430071

出　　处：《肿瘤防治研究》2024年第7期554-560,共7页Cancer Research on Prevention and Treatment

基　　金：国家自然科学基金(82274559);中央高校基本科研业务费专项资金资助(2042023kf0052)。

摘　　要：目的探讨叶酸修饰脂质体槲皮素对三阴性乳腺癌细胞增殖、凋亡的影响及潜在的调控机制。方法叶酸修饰脂质体槲皮素处理三阴性乳腺癌细胞MDA-MB-231后,CCK-8法检测细胞活力;平板克隆实验检测细胞增殖克隆能力;流式细胞术检测细胞凋亡、细胞活性氧(ROS)水平及线粒体膜电位的变化;Western blot检测酪氨酸蛋白激酶2(JAK2)-信号转导与转录激活因子3(STAT3)信号通路相关蛋白及凋亡相关蛋白的表达水平。结果叶酸修饰脂质体槲皮素抑制MDA-MB-231细胞增殖(P=0.023)、促进其凋亡(P<0.001),促进MDA-MB-231细胞线粒体膜电位坍塌(P=0.003),提升MDA-MB-231细胞内ROS水平(P=0.034),抑制JAK2和STAT3磷酸化水平(P<0.001),下调抗凋亡蛋白Bcl2、Bcl-xL表达(P=0.037,0.028),上调促凋亡蛋白Bax、Bak、Cyt C、Cleaved-Caspase-3表达(P<0.001)。结论叶酸修饰脂质体槲皮素抑制三阴性乳腺癌细胞MDA-MB-231增殖并诱导其凋亡,其作用机制可能与抑制JAK2/STAT3信号通路活化并激活线粒体凋亡途径有关。Objective To investigate the effect of folic acid–modified liposome quercetin(FLQ)on the proliferation and apoptosis of triple negative breast cancer(TNBC)cells and explore its underlying mechanism.Methods CCK-8 was used to detect the effect of FLQ on TNBC cell viability.Colony formation assay was conducted to detect the effect of FLQ on TNBC cell proliferation.Flow cytometry was performed to detect the effect of FLQ on TNBC cell apoptosis,the levels of intracellular ROS,and mitochondrial membrane potential.Western blot analysis was conducted to detect the expression levels of JAK2/STAT3 signaling pathway-related and apoptosis-related proteins.Results FLQ inhibited the proliferation and promoted the apoptosis of MDA-MB-231 cells(P=0.023,P<0.001).It promoted mitochondrial membrane potential collapse and increased the intracellular ROS levels of MDA-MB-231 cells(P=0.003,P=0.034);inhibited the phosphorylation levels of JAK2 and STAT3;upregulated the expression levels of the proapoptotic proteins Bax,Bak,cytochrome C,and Cleaved-Caspase-3(P<0.001,P<0.001);and downregulated the expression levels of the antiapoptotic proteins Bcl2 and Bcl-xL(P=0.037,0.028).Conclusion FLQ inhibits the proliferation and induces the apoptosis of MDA-MB-231 cells.These effects may be related to the activation of the mitochondrial apoptosis pathway through the inhibition of the JAK2/STAT3 signaling pathway.

关 键 词：三阴性乳腺癌 叶酸修饰脂质体槲皮素 线粒体凋亡途径 JAK2/STAT3信号通路 

分 类 号：R737.9[医药卫生—肿瘤]