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乳腺癌MCF-7细胞中葡萄糖依赖性降低凋亡并诱导自噬

Low glucose dependent decrease of apoptosis and induction of autophagy in breast cancer MCF-7 cells.

作者信息

Krętowski Rafał, Borzym-Kluczyk Małgorzata, Stypułkowska Anna, Brańska-Januszewska Justyna, Ostrowska Halina, Cechowska-Pasko Marzanna

机构信息

Department of Pharmaceutical Biochemistry, Medical University of Białystok, Mickiewicza 2A, 15-222, Białystok, Poland.

Department of Biology, Medical University of Białystok, Białystok, Poland.

出版信息

Mol Cell Biochem. 2016 Jun;417(1-2):35-47. doi: 10.1007/s11010-016-2711-4. Epub 2016 May 9.

Abstract

Cancer cells have developed a number of adaptation mechanisms involving the signal activation of the transduction pathways, which promotes the progression and metastasis. Our results showed that the percentage of apoptotic MCF-7 cells incubated in the low glucose medium for 48 h was lower in comparison to those cultured in the high glucose medium, despite the high expression of the proapoptotic transcription factor-CHOP. Furthermore, the MCF-7 cells incubated in the low glucose medium for 48 h showed a higher expression of NF-κB p100/p52 subunits compared to cells incubated in the high glucose medium. Moreover, our findings demonstrated that the shortage of glucose strongly induces autophagy in MCF-7 cells. The activation of this process is not associated with the changes in the expression of mTOR kinase. We suggest, that the antiapoptotic chaperone ORP150 induction, transcription factor NF-κB2 activation, and increased autophagy constitute mechanisms protecting the MCF-7 cells against apoptosis.

摘要

癌细胞已经形成了许多涉及信号转导通路激活的适应机制,这促进了肿瘤的进展和转移。我们的结果表明,尽管促凋亡转录因子CHOP高表达,但在低葡萄糖培养基中培养48小时的凋亡MCF-7细胞百分比低于在高葡萄糖培养基中培养的细胞。此外,与在高葡萄糖培养基中培养的细胞相比,在低葡萄糖培养基中培养48小时的MCF-7细胞显示出更高的NF-κB p100/p52亚基表达。此外,我们的研究结果表明,葡萄糖缺乏强烈诱导MCF-7细胞自噬。这一过程的激活与mTOR激酶表达的变化无关。我们认为,抗凋亡伴侣蛋白ORP150的诱导、转录因子NF-κB2的激活以及自噬增加构成了保护MCF-7细胞免受凋亡的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edf9/4887537/3b51ea1e65d0/11010_2016_2711_Fig1_HTML.jpg

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