SIRT1通过PI3K/AKT/mTOR失活来挽救自噬通量,抑制dox诱导的MCF-7细胞衰老。

IF 3.5 3区 生物学 Q3 CELL BIOLOGY
Ge Wu , Wei Yao , Lin Cheng , Xiaoping Wang , Tongsheng Chen
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引用次数: 0

摘要

Sirtuin 1 (SIRT1)是一种去乙酰化酶,因其在调节自噬、衰老、细胞代谢和肿瘤发生中的作用而被广泛研究。在这项研究中,我们研究了SIRT1如何调节阿霉素(DOX)诱导的乳腺癌细胞系MCF-7细胞的衰老。SIRT1显著降低dox诱导的衰老相关蛋白p53、p21和SA-β-Gal活性的升高,表明SIRT1抑制dox诱导的衰老。值得注意的是,SIRT1增加了dox诱导的p62积累上调,逆转了dox诱导的LC3II/LC3I比值的下降,表明SIRT1逆转了dox诱导的自噬通量阻断。自噬抑制剂氯喹(chloroquine, CQ)部分消除了SIRT1的抗衰老作用,说明自噬介导了SIRT1的抗衰老作用。此外,SIRT1抑制dox诱导的磷脂酰肌醇-3激酶(PI3K)/AKT/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的激活,从而促进自噬。PI3K抑制剂LY294002增强了SIRT1的抗衰老作用,而AKT激活剂SC-79则逆转了SIRT1的抗衰老作用。总之,我们的研究表明SIRT1通过灭活PI3K/AKT/mTOR通路来抵消dox诱导的MCF-7细胞衰老。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
SIRT1 rescues autophagic flux via PI3K/AKT/mTOR inactivation to suppress DOX-induced senescence in MCF-7 cells
Sirtuin 1 (SIRT1), a deacetylase, has been extensively studied for its roles in regulating autophagy, aging, cellular metabolism and tumorigenesis. In this study, we investigated how SIRT1 modulates doxorubicin (DOX)-induced senescence in MCF-7 cells, a breast cancer cell line. SIRT1 significantly reduced the DOX-induced elevation of senescence-associated proteins p53, p21, and SA-β-Gal activity, revealing that SIRT1 inhibited DOX-induced senescence. Notably, SIRT1 increased the DOX-induced upregulation of p62 accumulation and reversed the DOX-induced decrease in the LC3II/LC3I ratio, revealing that SIRT1 reversed the DOX-induced blockage of autophagic flux. The autophagy inhibitor chloroquine (CQ) partially abolished the anti-aging effects of SIRT1, indicating that autophagy mediated the anti-aging effects of SIRT1. Additionally, SIRT1 suppressed the DOX-induced activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway, thereby facilitating autophagy. The PI3K inhibitor LY294002 enhanced the anti-aging effect of SIRT1 which, however, was reversed by the AKT activator SC-79. In conclusion, our study reveals that SIRT1 counteracts DOX-induced senescence in MCF-7 cells by inactivating PI3K/AKT/mTOR pathway.
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来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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