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姜黄素对人肺腺癌细胞系A549具有诱导自噬的抗癌作用。

Curcumin induced autophagy anticancer effects on human lung adenocarcinoma cell line A549.

作者信息

Liu Furong, Gao Song, Yang Yuxuan, Zhao Xiaodan, Fan Yameng, Ma Wenxia, Yang Danrong, Yang Aimin, Yu Yan

机构信息

Department of Public Health, Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Department of Nuclear Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

出版信息

Oncol Lett. 2017 Sep;14(3):2775-2782. doi: 10.3892/ol.2017.6565. Epub 2017 Jul 8.

Abstract

To investigate the anticancer effects of curcumin-induced autophagy and its effects on the human lung adenocarcinoma A549 cell line, inverted phase contrast microscopy was used to observe alterations to the cytomorphology of cells. An MTT assay was used to measure cell viability. Autophagy was detected using acridine orange (AO) staining and 3-methyladenine (3-MA) was used as an autophagy-specific inhibitor. Dose- and time-dependent A549 cell viability inhibition was observed following curcumin treatment. A dose-dependent increase in the red fluorescent structures in A549 cells was identified following curcumin treatment for 48 h through AO staining. In addition, the activation of autophagy was determined through changes in the number of autophagic vesicles (AVs; fluorescent particles) infected with monodansylcadaverine (MDC). The fluorescence intensity and density of AVs in the curcumin-treated groups were higher at 48 h compared with the control group. Finally, the MTT assay demonstrated that the survival rates of the curcumin-treated cells were increased when pretreated with 3-MA for 3 h, indicating that the inhibitory effect of curcumin on A549 cells is reduced following the inhibition of autophagy. Furthermore, AO and MDC staining confirmed that 3-MA does inhibit the induction of autophagy. Thus, it was hypothesized that the induction of autophagy is partially involved in the reduction of cell viability observed following curcumin treatment. The anticancer effects of curcumin on A549 cells can be reduced using autophagy inhibitors. This suggests a possible cancer therapeutic application of curcumin through the activation of autophagy. These findings have improved the understanding of the mechanism underlying the anticancer property of curcumin.

摘要

为了研究姜黄素诱导的自噬的抗癌作用及其对人肺腺癌A549细胞系的影响,采用倒置相差显微镜观察细胞的细胞形态学变化。采用MTT法检测细胞活力。使用吖啶橙(AO)染色检测自噬,并使用3-甲基腺嘌呤(3-MA)作为自噬特异性抑制剂。姜黄素处理后观察到A549细胞活力受到剂量和时间依赖性抑制。通过AO染色发现,姜黄素处理48小时后,A549细胞中红色荧光结构呈剂量依赖性增加。此外,通过单丹磺酰尸胺(MDC)感染的自噬泡(AVs;荧光颗粒)数量的变化来确定自噬的激活。与对照组相比,姜黄素处理组在48小时时AVs的荧光强度和密度更高。最后,MTT试验表明,用3-MA预处理3小时后,姜黄素处理的细胞存活率增加,这表明抑制自噬后姜黄素对A549细胞的抑制作用降低。此外,AO和MDC染色证实3-MA确实抑制自噬的诱导。因此,推测自噬的诱导部分参与了姜黄素处理后观察到的细胞活力降低。使用自噬抑制剂可以降低姜黄素对A549细胞的抗癌作用。这表明姜黄素通过激活自噬可能具有癌症治疗应用。这些发现增进了对姜黄素抗癌特性潜在机制的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2f5/5588543/46dd1b41f441/ol-14-03-2775-g00.jpg

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