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Akt在玉竹凝集素诱导人非小细胞肺癌A549细胞凋亡和自噬中的分子开关作用

Molecular switch role of Akt in Polygonatum odoratum lectin-induced apoptosis and autophagy in human non-small cell lung cancer A549 cells.

作者信息

Li Chunyang, Chen Jie, Lu Bangmin, Shi Zheng, Wang Hailian, Zhang Bin, Zhao Kailiang, Qi Wei, Bao Jinku, Wang Yi

机构信息

School of Life Sciences and Key Laboratory of Bio-resources and Eco-environment, Ministry of Education, Sichuan University, Chengdu, China.

Central Laboratory of Clinical Medicine, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu, China.

出版信息

PLoS One. 2014 Jul 3;9(7):e101526. doi: 10.1371/journal.pone.0101526. eCollection 2014.

DOI:10.1371/journal.pone.0101526
PMID:24992302
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4081584/
Abstract

Polygonatum odoratum lectin (POL), isolated from traditional Chinese medicine herb (Mill.) Druce, has drawn rising attention due to its wide biological activities. In the present study, anti-tumor effects, including apoptosis- and autophagy-inducing properties of POL, were determined by a series of cell biology methods such as MTT, cellular morphology observation, flow cytometry, immunoblotting. Herein, we found that POL could simultaneously induce apoptosis and autophagy in human non-small cell lung cancer A549 cells. POL initiated apoptosis through inhibiting Akt-NF-κB pathway, while POL triggered autophagy via suppressing Akt-mTOR pathway, suggesting the molecular switch role of Akt in regulating between POL-induced apoptosis and autophagy. Moreover, ROS was involved in POL-induced inhibition of Akt expression, and might therefore mediate both apoptosis and autophagy in A549 cells. In addition, POL displayed no significant cytotoxicity toward normal human embryonic lung fibroblast HELF cells. Due to the anti-tumor activities, POL might become a potent anti-cancer drug in future therapy, which might pave the way for exploring GNA-related lectins into effective drugs in cancer treatment.

摘要

玉竹凝集素(POL)是从传统中药玉竹(Mill.)Druce中分离得到的,因其广泛的生物学活性而受到越来越多的关注。在本研究中,通过MTT、细胞形态观察、流式细胞术、免疫印迹等一系列细胞生物学方法,确定了POL的抗肿瘤作用,包括诱导凋亡和自噬的特性。在此,我们发现POL可同时诱导人非小细胞肺癌A549细胞凋亡和自噬。POL通过抑制Akt-NF-κB途径引发凋亡,而POL通过抑制Akt-mTOR途径触发自噬,提示Akt在调节POL诱导的凋亡和自噬之间的分子开关作用。此外,ROS参与了POL诱导的Akt表达抑制,因此可能介导A549细胞的凋亡和自噬。此外,POL对正常人胚肺成纤维细胞HELF细胞无明显细胞毒性。由于其抗肿瘤活性,POL可能成为未来治疗中一种有效的抗癌药物,这可能为探索GNA相关凝集素成为癌症治疗中的有效药物铺平道路。

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