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叶黄素通过PI3K/AKT/mTOR信号通路抑制A549人非小细胞肺癌细胞的生长并激活细胞凋亡。

Lutein Inhibits Cell Growth and Activates Apoptosis via the PI3K/AKT/mTOR Signaling Pathway in A549 Human Non-Small-Cell Lung Cancer Cells.

作者信息

Zhang Wen-Long, Zhao Ya-Nan, Shi Zhang-Zhen, Cong Dan, Bai Yuan-Song

机构信息

Department of Hematology and Oncology, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China, 130033.

出版信息

J Environ Pathol Toxicol Oncol. 2018;37(4):341-350. doi: 10.1615/JEnvironPatholToxicolOncol.2018027418.

Abstract

Cancer, the uncontrolled growth of cells, is a major disease that threatens the worldwide population. Among all cancer types, lung cancer has the highest morbidity rate, with a survival rate of less than 5%. Various studies have focused on discovering a potent anticancer drug that will increase the survival rate of lung cancer patients. Lutein (3,3'-dihydroxy-β, ε-carotene), a carotenoid present in fruits and vegetables, is one such compound that possesses excellent antioxidant properties. The present study was designed to determine the anticancer effect of lutein against A549, a non-small-cell lung cancer cell line. The cytotoxic effect of lutein against lung cancer cells (A549 and HCC827) and normal cells (BEAS-2B) was detected by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The Transwell assay was performed to detect the inhibitory potential of lutein against cell invasion and migration of A549 cells. The induction of apoptosis by lutein in A549 was analyzed by a double-staining technique using TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling) and DAPI (4',6-diamidino-2-phenylindole) staining assays to confirm the molecular mechanism exhibited by lutein to induce apoptosis through regulating the phosphoinositide 3-kinase (PI3K)/AKT signaling molecules that are often deregulated in cancerous condition. The results show that lutein inhibits the PI3K/AKT signaling pathway and induces apoptosis in A549, which may therefore be used as a potent natural anticancer drug with no side effects to treat lung cancer.

摘要

癌症,即细胞的无节制生长,是一种威胁全球人口的主要疾病。在所有癌症类型中,肺癌的发病率最高,生存率不到5%。各种研究都集中在发现一种有效的抗癌药物,以提高肺癌患者的生存率。叶黄素(3,3'-二羟基-β,ε-胡萝卜素)是一种存在于水果和蔬菜中的类胡萝卜素,是一种具有优异抗氧化特性的化合物。本研究旨在确定叶黄素对非小细胞肺癌细胞系A549的抗癌作用。通过MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐)法检测叶黄素对肺癌细胞(A549和HCC827)和正常细胞(BEAS-2B)的细胞毒性作用。进行Transwell实验以检测叶黄素对A549细胞侵袭和迁移的抑制潜力。通过使用TUNEL(末端脱氧核苷酸转移酶介导的dUTP缺口末端标记)和DAPI(4',6-二脒基-2-苯基吲哚)染色法的双重染色技术分析叶黄素在A549中诱导凋亡的情况,以确认叶黄素通过调节在癌症状态下经常失调的磷酸肌醇3-激酶(PI3K)/AKT信号分子来诱导凋亡所表现出的分子机制。结果表明,叶黄素抑制PI3K/AKT信号通路并诱导A549细胞凋亡,因此可能用作一种无副作用的有效天然抗癌药物来治疗肺癌。

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